INRC
INRC

Program Book 2020

• Back to schedule

International
Narcotics
Research
Conference

july 22–24
2020

Valencia ES

Program Book
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Program Book 2020

Photo credits: Brian Ruyle - Morón Lab

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Table of Content
Welcome to INRC 2020

4

Code of conduct

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Schedule7

Day 1 • July 22nd
Abstracts

911

Day 2 • July 23rd
Abstracts

19
21

Day 3 • July 24th
Abstracts

28
30

Sponsors

38

INRC 2020 Committees

39

INRC in 2021...

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Welcometo INRC 2020
Welcome to International
Narcotics Research Conference– INRC – conference in 2020!
Thank you for attending our very first
online conference. We are very pleased to
be able to hold our yearly meeting and welcome you to attend this amazing science
content despite the current challenges.
This year will honor our fantastic undergraduate, graduate students and postdoctoral researchers and give them the voice
they deserve to present their latest results.
Let’s enjoy some science.

⚠ Rules for the Conference:•••https://wustl-hipaa.zoom.us/j/91468020593?
pwd=MGtIenlsWUJNZjZGck93T0ZHaGJ4UT09•

Password: 009991•

Stay in Touch!
Check out our Website!
inrconference.org•

NO RECORDING. All talks will be recorded andavailable on our website for a limited amount oftime after the conference. It is very important toabide by these rules to encourage open communication and trust within our community.
Please do not distribute the links to the conference. We are trying our best to avoid being‘zoom-bombed’ by not distributing them widely.
Anyone who wants to attend can register here
for $5. If it’s an issue of money, please email us atinternationalnarcoticsresearch@gmail.com andwe are happy to provide a code to waive the fee.
Please be respectful in all comments and interactions. The INRC Committee will not allow any
form of disrespect or discrimination at our conferences. Any issues can be reported to internationalnarcoticsresearch@gmail.com. Please see
our Code of Conduct for further details.
Keep yourself muted during all talks to limit background noise.
To ask questions during webinars, please use
the “Q&A” function. These questions will be considered by the moderators to ask the speaker.
Please use the “Chat” function for any other comments pertaining to the talk.
Have fun and enjoy the science.

Join our Slack Community!
Follow us on Twitter!
@INRCmeeting

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Code of conduct

INRC upholds a strong codeof conduct to protect andencourage scientists toshare their work. The Code of
Conduct aims to outline this andincrease the conversations andcollaborations around scientifictopics. This Code applies to all
platforms hosted by the INRC.

Recording Restrictions
Presentations will be recorded by the INRC forrebroadcast with permission from presenters andposted on the INRC website with restricted access(password protected) for attendees who can notparticipate during the live session. Unauthorizedrecordings by attendees will not be allowed. Prior
to quoting or publishing any information presented at a conference in any publication, written
or electronic, written approval of the contributing
member must first be obtained.
Without previous written consent of the contributing member, the audio or video recording oforal presentations and discussions, the photography/screen-shooting of slides, and printed orelectronic quotes from papers, during the conference is strictly prohibited.
These restrictions apply to each attendee and areintended to cover social networks, blogs, tweets
or any other publication, distribution, communication or sharing of information presented or discussed at the conference.
Each attendee acknowledges and agrees to theserestrictions when registration is accepted and asa condition of being permitted to attend.
Each attendee assumes sole responsibility forthe protection and preservation of any intellectual
property rights in such member’s contributions to
a conference. If you become aware of someone
making unauthorized recordings, please immediately email this information to:internationalresearchconference@gmail.com.

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Unauthorized Sharing of Conference
Links
Our attendance is limited to license constraints.
To ensure that all attendees can access the meeting access to the conference must be limited topaid registration. Sharing the access links withanyone is thus prohibited. Individuals must register individually and can ask for a fee waiver ifnecessary.

Virtual Conference Best Practices
To avoid unwanted disruptions (i.e. “zoom-bombing”) attendees should not share any links to thevirtual conference rooms. Attendees, unless presenting, will turn their microphones/cameras off.
Any questions addressed to the speaker should betyped in the chat window. Moderators will selectquestions within this chat window and share themwith the speaker according to the time remaining
within the time allotted. Cameras may be on or off
depending on personal choice, although keeping
your camera on may foster a better experience forthe speaker as they deliver their talk to the audience. A virtual background will be shared with the
speakers if they decide to use it.

Inappropriate Behavior Policy
The INRC has always been encouraging open andhonest intellectual debate as part of a welcoming
and inclusive atmosphere. The INRC will foster
rigorous analysis of all science presented or discussed in a manner respectful to all attendees. To
help maintain an open and respectful communityof scientists, the INRC does not tolerate illegal,
disrespectful or inappropriate behavior, including harassment of any kind. The INRC condemns
inappropriate or suggestive acts or commentsthat demean another person by reason of his or
her gender, gender identity or expression, race,
religion, ethnicity, age or disability or that are
unwelcome or offensive to other members of thecommunity or their guests. Any allegations of any
such behavior will be considered and analyzed
by the INRC committee on a case by case basis,and violations will result in immediate removalfrom the conference. Please report inappropriate
behavior to:internationalnarcoticsresearch@gmail.com.
If any member of the INRC board becomes awareof illegal or inappropriate behavior, the member
will report this to the rest of the INRC board.
Immediate reporting is important to allow theINRC the opportunity to properly assess the situation and fashion an appropriate response that
addresses the problem while being sensitive tothe concerns of all who are affected. Those who
violate this policy will be removed from participating in the conference to the best of the INRC
board’s capability.

Privacy Policy
The INRC is committed to protecting the privacyof its website visitors and conference attendees.
Attendee information will not be shared unlessgiven explicit permission.

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https://wustl-hipaa.zoom.us/j/91468020593?
pwd=MGtIenlsWUJNZjZGck93T0ZHaGJ4UT09

Password: 009991

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J U LY

EasternTime

WED

Schedule

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J U LYTHU

24
J U LY

FRI

11:00am
11:10amIqira Saeed

Manish K. Madasu

Anna Gutridge

Michelle Morochnik

Sam Groom

Arryn Blaine

Alexander French

Sweta Adhikary

Samuel Singleton

Sarah C. Simmons

Jade Degrandmaison

Farhana Sakloth

Susan Ahmedyar

Julia K. Brynildsen

Javier Cuitavi

Dani CaoBesma Benredjem

Eden Anderson

Moriah L. Jacobson

Zoë Dworsky-Fried

Gregory Grecco

Valentina Martinez DamonteSineadh M. Conway

Lani Tieu

Courtney A. Bouchet

Kaitlin C. Reeves

David Reiner

Bryan Sears

Crystal Lemchi

Darrell Eacret

Zachariah Bertels

Devan Gomez

Marwa Mikati

Evan F. Fullerton

INRC Welcome Reception

11:20am
11:30am
11:40am
11:50am
12:00pm
12:10pm
12:20pm
12:30pm
12:40pm
12:50pm
1:00pmLauren C. Smith

Benjamin M. Clements

Ethan M. Anderson

Sarah Palumbo

1:10pm1:20pmMatthew S. Scarnati
1:30pmHannah Frye

Round Table (1hour)
Academic and Industry Career

Tamara Markovic
Kylie B. McPherson

1:40pmShijia Liu

Virtual INRC Closure

Jacob A. Beierle

Valencia Announcement

1:50pm
2:00pm

INRC Welcome | Goodbye, Opioid Signaling, Reward—Addiction, Pain–Analgesia, Kappa, Round Table

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22
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Eastern
Time

WED

23
J U LYTHU

24
J U LY

FRI

11:00am
11:10am

Talk: Larry Toll

11:20amModerators:
Gregory Corder
Tuan Trang

11:30amModerators:
Ream Al-Hasani
Lee-Yuan Liu-Chen

11:40am
11:50am
12:00pm

Moderators:
Larry Toll
Maritxell Canals

12:10pm
12:20pm

Moderators:
Thomas Kash
Lucia Hipolito

12:30pm
12:40pm
12:50pm

Moderators:
Catherine Cahill
Nicolas Massaly

1:00pm1:10pm1:20pm
1:30pmModerators:
Emily Jutkiewicz
Jose Moron-Concepcion
Round Table (1hour)
Academic and Industry Career

1:40pmVirtual INRC Closure
1:50pmValencia Announcement
2:00pm

INRC Welcome | Goodbye, Opioid Signaling, Reward—Addiction, Pain–Analgesia, Kappa, Round Table

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Introduction
11: 0 0 a m – 11: 2 0 a m

Larry Toll

12 : 0 0 p m – 12 :10 p m

Besma Benredjem
In vitro signaling profiles of opioid ligands allow to infer
their clinical responses
12 :10 p m – 12 : 2 0 p m

Talks session #1
11: 2 0 a m – 12 : 3 0 p m

Opioid Signaling

Moderators:

Larry Toll
Meritxell Canals

Speakers:
11: 2 0 a m – 11: 3 0 a m

Sam Groom
A novel G protein-biased agonist at the μ opioid receptor
induces substantial receptor desensitization through GRK
11: 3 0 a m – 11: 4 0 a m

Sweta Adhikary
Mu opioid receptors regulate adenosine tone in stratal
Synapses
11: 4 0 a m – 11: 5 0 a m

Jade Degrandmaison
In vivo mapping of the delta-opioid receptor interactomeusing knock-in mice
11: 5 0 a m – 12 : 0 0 p m

Julia K. Brynildsen
Gene coexpression patterns predict opiate-induced brain
state transitions

Zoë Dworsky-Fried
Central amygdala inflammation drives pain hypersensitivity and impaired opioid signalling in a mouse model ofmultiple sclerosis
12 : 2 0 p m – 12 : 3 0 p m

Sineadh M. Conway
Developing a novel approach for in vivo electrochemical
detection of opioid peptides

Talk session #2
12 : 3 0 p m – 2 : 0 0 p m

Reward – Addiction

Moderators:

Emily Jutkiewicz
Jose Moron-Concepcion

Speakers:
12 : 3 0 p m – 12 : 4 0 p m

Kaitlin C. Reeves
Mu opioid receptors on vGluT2-expressing glutamatergic
neurons modulate opioid reward
12 : 4 0 p m – 12 : 5 0 p m

Crystal Lemchi
Development of a Novel Neonatal Opioid Exposure Modelin Mice9

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12 : 5 0 p m – 1: 0 0 p m

Devan Gomez
Mesolimbic subcicruit-specific adaptations following
protracted morphine withdrawal and altered motivatedbehavior
1: 0 0 p m – 1:10 p m

Lauren C. Smith
Validation of a nicotine vapor self-administration model inrats with relevance to electronic cigarette use
1:10 p m – 1: 2 0 p m

Ethan M. Anderson
HDAC5 in the rat nucleus accumbens suppresses cuedand drug-primed reinstatement of heroin seeking in a D1
vs D2 cell type-specific manner
1: 2 0 p m – 1: 3 0 p m

Matthew S. Scarnati
Differential sensitivity of human neurons carrying μ opioid receptor (MOR) N40D variants in response to ethanol
1: 3 0 p m – 1: 4 0 p m

Hannah FryeSex Differences in the Role of Cornichon Homolog-3 on
Opioid Use Disorder Risk and Spatial Memory
1: 4 0 p m – 1: 5 0 p m

Shijia Liu
Neural basis of opioid-induced respiratory depression
and its rescue
1: 5 0 p m – 2 : 0 0 p m

Jacob A. Beierle
Differences in oxycodone state dependent learning
between nearly isogenic BALB/cJ and BALB/cByJ mouse
substrains map to chromosomes 14 and 6

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Sam Groom

Sweta Adhikary

Sam Groom*, Nina Kathleen Blum, Alex Conibear,Alex Disney, Stephen Husbands, Yangmei Li,
Lawrence Toll, Stefan Schluz, Graeme Henderson,
Eamonn Kelly, Chris Bailey

Sweta Adhikary*, John T. Williams, & William T.
Birdsong

Ph.D. Student

A novel G protein-biased agonistat the μ opioid receptor induces
substantial receptor desensitization
through GRKMy recent work has determined that the cyclic
endomorphin analogue Tyr-c[D-Lys-Phe-Tyr-Gly](Compound 1) is a novel G protein-biased agonistat the μ opioid receptor. Surprisingly, we foundthat Compound 1 induces considerable desensitization of the μ opioid receptor in rat locus coeruleus neurons. Compound 1-induced receptor
desensitization occurred through GRK in spite ofits G protein-biased pharmacology. Our findings
cast doubt on the assumption that G protein-biased agonists will categorically evade receptor
desensitization and tolerance.

Graduate Student

Mu opioid receptors regulate adenosine tone in stratal Synapses
Activation of mu opioid receptors inhibits adenosine tone in striatal synapses through a cAMP
mediated pathway. Selectively knocking-out mu
opioid receptors from pre or post synaptic compartments does not augment adenosine tone in
the presence of morphine, but a global mu knockout does. Additionally, adenosine is regulated
by postsynaptic medium spiny neurons in the
striatum.

Day 1 • July 22nd
Session #1, Talk #1

Day 1 • July 22nd
Session #1, Talk #2

Opioid Signaling

Opioid Signaling

11: 2 0 a m – 11: 3 0 a m

11: 3 0 a m – 11: 4 0 a m

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Jade Degrandmaison

Julia K. Brynildsen

Jade Degrandmaison*, Khaled Abdallah,
Véronique Blais, Samuel Génier, Marie-Pier
Lalumière, Francis Bergeron, Catherine M. Cahill,
Jim Boulter, Christine L. Lavoie, Jean-Luc Parent
and Louis Gendron

Julia K. Brynildsen*, Kyla D. Mace, Eli J. Cornblath,
Carmen Weidler, Fabio Pasqualetti, Danielle S.
Bassett, and Julie A. Blen

Ph.D. Candidate

In vivo mapping of the delta-opioid
receptor interactome using knock-in
mice
Despite its significant potential as a therapeutictarget for chronic pain management, our understanding of the molecular and cellular mechanisms regulating the trafficking and signaling of
the delta-opioid receptor (DOPr) remains fragmentary. Using brain homogenates from our
newly generated FLAG-DOPr-KO (knock-out) and
FLAG-DOPr-KI (knock-in) mouse models, we identified several novel endogenous DOPr interactors
involved in protein folding, trafficking, and signaltransduction, as well as other proteins belonging to the receptors/channels/transporters family.
We also describe the generation of a conditional
KI FLAG-DOPr mouse line, an invaluable tool toinvestigate DOPr functions in specific neuron populations and circuits.

Ph.D. Candidate

Gene coexpression patterns predict
opiate-induced brain state transitions
Reconfiguration of neuronal connectivity may
explain heightened opioid abuse liability in individuals with a history of chronic drug exposure.
To characterize network-level changes in neuronal
activity induced by chronic opiate exposure, weconstructed network models from FOS expression data in mice that are morphine-naïve, morphine-dependent, or have undergone 4 weeks
of withdrawal from chronic morphine exposure.
We demonstrate that basal gene expression patterns are predictive of changes in FOS correlation networks in the morphine-dependent stateand identify key brain regions that are particularly influential in driving transitions between opiate-naïve and opiate-dependent brain states.

Day 1 • July 22nd
Session #1, Talk #3

Day 1 • July 22nd
Session #1, Talk #4

Opioid Signaling

Opioid Signaling

11: 4 0 a m – 11: 5 0 a m

11: 5 0 a m – 12 : 0 0 p m

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Besma BenredjemZoë Dworsky-Fried

Besma Benredjem*, Jonathan Gallion, Dennis
Pelletier, Paul Dallaire, Johanie Charbonneau,
Darren Cawkill, Karim Nagi, Mark Gosink, Viktoryia
Lukashova, Stephen Jenkinson, Yong Ren,
Christopher Somps, Brigitte Murat, Emma Van Der
Westhuizen, Christian Le Gouill, Olivier Lichtarge,
Anne Schmidt, Michel Bouvier, Graciela Pineyro

Zoë Dworsky-Fried*, Bradley J Kerr, Anna MW
Taylor

Ph.D. Student

In vitro signaling profiles of opioid
ligands allow to infer their clinicalresponses
We have developed a method that uses preclinical responses of well-known prescription opioids
and of novel molecules to classify them according to similarities in their signaling profiles. We
have found that the categories that result fromthis classification are associated with different
degrees of clinically reported side effects (suchas respiratory depression). This method could
help to identify better drug candidates, allowing
to advance to clinical testing only those with lessside effects potential.

M.S.c Student

Central amygdala inflammation
drives pain hypersensitivity andimpaired opioid signalling in a mousemodel of multiple sclerosis
Chronic pain is one of the most frequent anddebilitating symptoms associated with the autoimmune disorder multiple sclerosis (MS). In thisstudy, we use a mouse model of MS to show that
inflammation within the central amygdala alters
anti-nociceptive signalling leading to blunted opioid analgesia. Our data identify a novel mechanism for impaired pain control in autoimmune
disorders and highlight potential strategies, suchas targeting inflammation, to improve analgesic
efficacy in MS.

Day 1 • July 22nd
Session #1, Talk #5

Day 1 • July 22nd
Session #1, Talk #6

Opioid Signaling

Opioid Signaling

12 : 0 0 p m – 12 :10 p m

12 :10 p m – 12 : 2 0 p m

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Sineadh M. Conway

Kaitlin C. Reeves

Sineadh M. Conway*, Graydon B. Gereau, Loc
V. Thang, John R. Cirrito, Carla M. Yuede, Ream
Al-Hasani

Kaitlin C. Reeves*, Megan J. Kube, Gregory G.
Grecco, Brandon M. Fritz, Braulio Muñoz, Fuqin
Yin, Yong Gao, David L. Haggerty, Hunter J.
Hoffman, Brady K. Atwood

Postdoctoral Researcher

Developing a novel approach for invivo electrochemical detection of
opioid peptides
The endogenous opioid peptide systems are critical for analgesia, reward processing, and negative
affect, however research on their in vivo function
in modulation of these behaviors has been challenging due to an inability to reliably and consistently detect dynamic changes in opioid peptides.
To fill this gap, we have developed microimmunoelectrodes (MIEs) for rapid and sensitive detectionof opioid peptides. Using square wave voltammetry, we show that dynorphin antibody-coated MIEs
are sensitive and selective to increasing concentrations of dynorphin in the fmol range, and weare currently working to demonstrate the utilityof these MIEs both in vitro via brain slice preparation and in vivo for real-time, rapid detection ofendogenous opioid peptide release in awake andbehaving animals.

Ph.D. Candidate

Mu opioid receptors on vGluT2-expressing glutamatergic neurons
modulate opioid reward
The role of mu opioid receptor (MOR)-mediatedregulation of GABA transmission in opioid reward
is well established, but much less is known about
MOR-mediated regulation of glutamate transmission and how this relates to drug reward; therefore,
we created a transgenic mouse that lacks MORs in
vGluT2-expressing neurons (MORflox-vGluT2cre).
Compared to wild-type littermate controls, these
MORflox-vGluT2cre mice have disrupted opioid
reward, consume less oxycodone, lack oxycodone-induced locomotor stimulation, and display baseline withdrawal-like responses following
the development of oxycodone dependence.
However, other MOR-mediated behaviors, including oxycodone-induced analgesia, are unaffected,
suggesting that MOR-mediated regulation of glutamate transmission plays a specific role in opioid
reward and withdrawal.

Day 1 • July 22nd
Session #1, Talk #7

Day 1 • July 22nd
Session #2, Talk #1

Opioid Signaling

Reward – Addiction

12 : 2 0 p m – 12 : 3 0 p m

12 : 3 0 p m – 12 : 4 0 p m

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Crystal Lemchi

Devan Gomez

Crystal Lemchi*, Amelia Dunn, Juliet Mengaziol,
Shivon Robinson and Julie A. Blendy

Devan Gomez*, Matthew Hearing

Ph.D. Candidate

Development of a Novel Neonatal
Opioid Exposure Model in Mice
The long-term effects of chronic opioid exposure
during early life are not well characterized due
to many confounding factors in human studies
and lack of consistency in animal models. Ourlab has created a novel mouse model of opioid
exposure [spanning both in utero and PND 1-14],
which encompasses the human equivalent of“three-trimester” opioid exposure and recapitulates characteristic phenotypes associated withNOWS during both development and withdrawal.
Despite this robust withdrawal, preliminary results
suggest few long-term behavioral consequences(CPP, LH,TST) of this NOWS model.

Graduate Student

Mesolimbic subcircuit-specificadaptations following protracted
morphine withdrawal and altered
motivated behavior
Our lab has found that protracted withdrawal
from a dependence-inducing regimen of morphine reduces excitation and increases GABAARmediated inhibition within a subpopulationof lateral VTA dopamine neurons projecting to
the lateral NAc shell. These adaptations alignwith preliminary findings suggesting that priorinduction of dependence increases subsequent
motivation for intravenously available morphineat this protracted withdrawal time point. These
data underscore the significance of distinguishing
functional differences between dopaminergic circuitry and their potential to separately contributeto neurobehavioral alterations related to opioid
withdrawal, relapse and shifts in motivated statesthat drive drug-seeking.

Day 1 • July 22nd
Session #2, Talk #2

Day 1 • July 22nd
Session #2, Talk #3

Reward – Addiction

Reward – Addiction

12 : 4 0 p m – 12 : 5 0 p m

12 : 5 0 p m – 1: 0 0 p m

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Lauren C. Smith

Ethan M. Anderson

Lauren C. Smith*, Marsida Kallupi, Lani Tieu, Kokila
Shankar, Abigail Jaquish, Jamie Barr, Yujuan Su,
Nathan Velarde, Sharona Sedighim, Lieselot L.
G. Carrette, Mike Klodnicki, Xin Sun, Giordano de
Guglielmo, Olivier George

Ethan M. Anderson*, Evgeny Tsvetkov, Allison
Galante, Makoto Taniguchi, and Christopher W.
Cowan

Graduate Student

Validation of a nicotine vapor self-administration model in rats with relevance to electronic cigarette use
There is currently no rodent model of nicotine
vapor self-administration, so we developed anovel model of voluntary electronic cigaretteuse in rats using operant behavior. We foundthat rats voluntarily exposed themselves to nicotine vapor to the point of reaching blood nicotine
levels that are similar to humans. Moreover, nicotine vapor self-administration resulted in addiction-like behaviors, including somatic signs ofwithdrawal, allodynia, anxiety-like behavior, andrelapse-like behavior after 3 weeks of abstinence.
These findings validate a novel animal model of
nicotine vapor self-administration in rodents
with relevance to electronic cigarette use in
humans and demonstrate the addictive properties and harmful effects of chronic nicotine vapor
self-administration.

Research Assistant Professor

HDAC5 in the rat nucleus accumbens
suppresses cued and drug-primed
reinstatement of heroin seeking in a
D1 vs D2 cell type-specific mannerHistone deacetylase 5 (HDAC5) is an epigenetic regulator that shuttles between the nucleus
and cytoplasm following drug exposure andalters intrinsic excitability of medium spiny neurons (MSNs) in the nucleus accumbens (NAc).
Here, using overexpression and knockdown
manipulations of HDAC5 in the rat NAc, I show
bi-directional effects of HDAC5 on 3 types of heroin-seeking behavior following several weeks ofheroin self-administration. Finally, I show thatoverexpression of HDAC5 reduces cue-induced
reinstatement when selectively expressed in
D1-MSNs and this same HDAC5 overexpressionin D2-MSNs reduces heroin-primed reinstatement
selectively; importantly, these results suggest thatthe current dogma concerning opposing roles of
D1 vs D2-MSNs on drug-seeking behavior may
be incomplete and these separable MSNs may
instead have complimentary roles in drug-seeking behavior.

Day 1 • July 22nd
Session #2, Talk #4

Day 1 • July 22nd
Session #2, Talk #5

Reward – Addiction

Reward – Addiction

1: 0 0 p m – 1:10 p m

1:10 p m – 1: 2 0 p m

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Matthew S. Scarnati

Hannah Frye

Matthew S. Scarnati*, Andrew J.,Boreland, Marisa
Joel, Ronald P. Hart, Zhiping P. Pang

Hannah E. Frye*, Yukitoshi Izumi, Min-Yu Sun,
Sidney B. Williams, Christopher R. Trousdale,
Alexis N. Harris, Andrew D. Sauerbeck, Terrance T.
Kummer, Steven Mennerick, Charles F. Zorumski,
Elliot C. Nelson, Joseph D. Dougherty, Jose A.
Morón

Postdoctoral Researcher

Differential sensitivity of humanneurons carrying μ opioid receptor(MOR) N40D variants in response toethanol
There is a limited understanding of the precise
cellular and molecular mechanisms underlying
AUD in humans. A functional polymorphism of
the mu-opioid receptor (MOR) N40D may alter therisk of developing AUD. iPS and induced neuronal(iN) cell technology provide unique opportunities
to model AUD in a human context. Alcohol application reveals that the MOR genotype confers
differential sensitivity to synaptic output which
depends on ethanol exposure time and concentration for AD-iNs and may help explain alcohol
dependence in individuals who carry the MOR
D40 SNP.

Graduate Student

Sex Differences in the Role of Cornichon Homolog-3 on Opioid Use
Disorder Risk and Spatial Memory
Single nucleotide polymorphisms (SNPs)in CNIH3, the gene which encodes for the AMPA
receptor (AMPAR) auxiliary protein cornichon
homolog-3 (CNIH3), are correlated with reduced
risk of opioid use disorder in humans. New datasuggest this correlation is stronger in women, andin mouse studies CNIH3 only affects spatial memory, hippocampal synaptic plasticity, and synaptic
density in females during the metestrus stage ofthe estrous cycle. Our study defines a sex-specific role for CNIH3 in spatial memory formationand synaptic plasticity, which are highly involvedin opioid use disorder and relapse.

Day 1 • July 22nd
Session #2, Talk #6

Day 1 • July 22nd
Session #2, Talk #7

Reward – Addiction

Reward – Addiction

1: 2 0 p m – 1: 3 0 p m

1: 3 0 p m – 1: 4 0 p m

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Shijia Liu

Jacob A. Beierle

Shijia Liu*, Dongil Kim, Tae Gyu Oh, Gerald Pao,
Jonghyun Kim, Richard D. Palmiter, Ronald M.
Evans, Sung Han.

Jacob A. Beierle*, Emily Yao, Julia Scotellaro, Gary
Peltz, Camron D. Bryant

Ph.D. Candidate

Neural basis of opioid-induced respiratory depression and its rescue
Opioid-induced respiratory depression (OIRD)
is the direct cause of the rapidly evolving opioid
crisis, yet its underlying neurobiological mechanisms are not well understood. We identify thata genetically defined neuronal population in thelateral parabrachial nucleus expressing µ-opioid
receptors (PBLOprm1 neurons) are involved in regulating breathing rhythm and OIRD pathogenesis.
In addition, we find that activating PBLOprm1 neurons via artificial and endogenous G-protein coupled receptor signaling pathways rescues OIRD,
thereby providing insights on novel therapeuticinterventions of OIRD in humans.

Graduate Student

Differences in oxycodone state
dependent learning between nearly
isogenic BALB/cJ and BALB/cByJ
mouse substrains map to chromosomes 14 and 6
Variation in subjective sensitivity to the rewarding
effects of opioids is heritable and can influence
addiction liability. In inbred BALB/c substrains we
identified robust differences in state-dependent
retrieval of oxycodone conditioned reward, but
not drug-free reward as measured via conditioned
place preference. Because these substrains areover 99% isogenic, identification of the genetic
factors influencing this trait is greatly facilitatedcompared to traditional F2 crosses. I will discuss
identification of 2 major-effect QTLs influencing
state dependent learning/retrieval of oxycodone
reward on proximal chromosome 14, and a female
specific locus on chromosome 6 as well as thelimited number of candidate genes that lie underneath these loci.

Day 1 • July 22nd
Session #2, Talk #8

Day 1 • July 22nd
Session #2, Talk #9

Reward – Addiction

Reward – Addiction

1: 4 0 p m – 1: 5 0 p m

1: 5 0 p m – 2 : 0 0 p m

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• Back to scheduleDay 2 • July 23rd

Talks session #3
11: 0 0 a m – 11: 5 0 a m

Talks session #4
11: 5 0 a m – 1: 0 0 p m

Pain – Analgesia

Reward – Addiction

Moderators:

Moderators:

Speakers:

Speakers:

Gregory Corder
Tuan Trang

11: 0 0 a m – 11:10 a m

Iqira Saeed
Can opioid exposure alter cancer incidence?
11:10 a m – 11: 2 0 a m

Anna Gutridge
Pharmacological Characterization of Natural and
Synthetic Akuamma Alkaloids for Pain Therapeutics
11: 2 0 a m – 11: 3 0 a m

Arryn Blaine
Investigating the Cellular and Behavioral Effects of δ-Opioid Receptor Mediated β-arrestin 1 Signaling

Thomas Kash
Lucia Hipolito

11: 5 0 a m – 12 : 0 0 p m

Javier Cuitavi
Microglia-mediated Mu Opioid Receptor alterations? A
new insight into pain-induced alcohol relapse in femalerats
12 : 0 0 p m – 12 :10 p m

Eden Anderson
Opioid self-administration induced sex-specific medial
prefrontal cortex plasticity and deficits in cognitive
flexibility
12 :10 p m – 12 : 2 0 p m

Gregory Grecco

Samuel Singleton

Prenatal Methadone Exposure Disrupts Neurobehavioral
Development

TRV130 partial agonism and capacity to produce analgesic tolerance revealed through reducing available mu opioid receptor number

Lani Tieu

11: 3 0 a m – 11: 4 0 a m

11: 4 0 a m – 11: 5 0 a m

Farhana Sakloth
In Vivo Evidence that Positive Allosteric Modulators of theμ-Opioid Receptor Enhance the Antinociceptive Efficacy
of Clinically Used Opioids, but not the Adverse Effects
Associated with their Repeated Administration

12 : 2 0 p m – 12 : 3 0 p m

Identification of Individual Differences in Response to
Methadone, Buprenorphine, and Naltrexone in an Animal
Model of Opioid Use Disorder
12 : 3 0 p m – 12 : 4 0 p m

David ReinerRole of projections between piriform and orbitofrontal
cortex in relapse to fentanyl seeking after food choice-induced voluntary abstinence

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12 : 4 0 p m – 12 : 5 0 p m

Darrell Eacret
Investigations into the behavioral and molecular consequences of chronic opioids and the relationship to disrupted sleep
12 : 5 0 p m – 1: 0 0 p m

Marwa Mikati
In vivo detection of endogenous opioid peptides and theirrole in opioid withdrawal syndrome

Round Table
1: 0 0 p m – 2 : 0 0 p m

Moderators:
Andrea Bedini

Assistant professor, University of Bologna

Lucia Hipolito
Associate professor, University of Valencia

Ream Al-Hasani
Assistant professor, St Louis College of Pharmacy

Jose Moron-Concepcion
Professor, Washington University in St. Louis

Amynah Pradhan
Associate Professor, University of Illinois in Chicago

John Streicher
Assistant professor, University of Arizona

Katherine Martucci
Assistant professor, Duke University

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Iqira Saeed

Anna Gutridge

Can opioid exposure alter cancer
incidence?

Gutridge AM*, Hennessy MR, Argade MD, Rhoda
ES, Royer QH, Riley AP, van Rijn RM

Ph.D. Student

There is considerable controversy regardingwhether opioids influence cancer-related outcomes in patients with pre-existing cancer. Less
work has explored whether opioid exposure
increases the risk of cancer-related outcomes in
opioid users who were initially free from cancer.
We report a systematic review which examines
the relationship between opioid exposure andcancer outcomes in populations of individuals
who were cancer-free prior to opioid exposure.

Graduate Student

Pharmacological Characterizationof Natural and Synthetic Akuamma
Alkaloids for Pain Therapeutics
Picralima nitida, commonly known as akuamma,
is a tree that produces opioidergic alkaloids(Menzies et al., Eur. J. Pharmacol.1998) and isused most generally for its analgesic and anti-inflammatory properties (Erharuyi et al., Asian Pac.
J. Trop. Med. 2014). Due to their ability to agonize the µ-opioid receptor (Menzies et al., Eur. J.
Pharmacol. 1998), I hypothesized these alkaloids
can be used in the treatment of pain. Six akuamma alkaloids were pharmacologically characterized at the µ-, δ- and κ- opioid receptors (µOR,δOR, κOR) for binding affinity and biased signaling
activity, and the compounds with the highest µOR
potency were then tested for analgesic properties
in nociception paradigms.

Day 2 • July 23rd
Session #3, Talk #1

Day 2 • July 23rd
Session #3, Talk #2

Pain – Analgesia

Pain – Analgesia

11: 0 0 a m – 11:10 a m

11:10 a m – 11: 2 0 a m

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Arryn Blaine

Samuel Singleton

Arryn Blaine*, Dr. Richard van Rijn, Rebecca Liu

Samuel Singleton*, Daniel Baptista-Hon, Emily
Edelston, Kirsty McCaughey, Ewan Camplisson,
Tim G Hales

Graduate Student

Investigating the Cellular and Behavioral Effects of δ-Opioid Receptor
Mediated β-arrestin 1 Signaling
Opioids targeting the delta opioid receptor havebeen investigated as alternative analgesic strategy to avoid adverse effects observed with mu
opioids. Unfortunately, delta opioids have a tendency to induce seizures, a severe side effectlinked to arrestin signaling. Here I investigatedseizure severity and ERK signaling by delta opioids with different arrestin efficacy in male andfemale wild-type, beta-arrestin 1 and beta-arrestin 2 KO mice.

Ph.D. Student

TRV130 partial agonism and capacity to produce analgesic tolerance
revealed through reducing available
mu opioid receptor number
The possibility that β-arrestin2 recruitment to mu
receptors may contribute to opioid side effects led
to the development of TRV130, a biased agonist in
favour of G-protein signalling. However, apparent
bias may be confounded by receptor overexpression. We examined the efficacies and apparent
potencies of mu agonists with full and partial receptor availability following exposure to the irreversible
mu antagonist β-FNA. In vivo, we also assessed
whether receptor number influenced the development of analgesic tolerance using heterozygous
mice expressing 50% fewer mu receptors. TRV130
was a very weak partial agonist in vitro even without
prior exposure to β-FNA. TRV130 was highly potent
and caused no analgesic tolerance in wild type mice.
In heterozygous mice, TRV130 was equally efficacious but caused profound tolerance after only 4days. These findings emphasise the need for consideration of receptor reserve when characterising
new opioid agonists. Furthermore, they suggest thebeneficial side effect profile of reportedly biased
agonists may be a result of partial agonism.

Day 2 • July 23rd
Session #3, Talk #3

Day 2 • July 23rd
Session #3, Talk #4

Pain – Analgesia

Pain – Analgesia

11: 2 0 a m – 11: 3 0 a m

11: 3 0 a m – 11: 4 0 a m

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• Back to scheduleFarhana Sakloth

Javier Cuitavi

Farhana Sakloth*, Kerri Pryce, Hye Jin Kang,
Abhijeet Kapoor, Tao Che, Lihuai Qin, Feodora
Bertherat, H. Ümit Kaniskan, Jian Jin, Bryan Roth,
Venetia Zachariou, and Marta Filizola

Javier Cuitavi*, Jesús David Lorente, Yolanda
Campos-Jurado, Natalia Landsberg and Lucía
Hipólito

Postdoctoral Researcher

In Vivo Evidence that Positive
Allosteric Modulators of the μ-Opioid
Receptor Enhance the Antinociceptive Efficacy of Clinically Used
Opioids, but not the Adverse Effects
Associated with their Repeated
Administration
We report two small molecules from a chemical
series of Positive allosteric modulators (PAMs) of
the µ-opioid receptor (MOR) exhibiting: (a) opposite biased signaling in vitro; (b) a differential
enhancement of the antinociceptive efficacy ofoxycodone, morphine, and methadone in mousemodels of pain, and (c) a lack of potentiation ofan unwanted side effect resulting from excessive
opioid administration. This series of MOR PAMs
holds promise for the development of adjuncts toopioid therapy to mitigate against overdose andopioid use disorders.

Ph.D. Student

Microglia-mediated Mu Opioid
Receptor alterations? A new insight
into pain-induced alcohol relapse infemale rats
Microglia play a role in pain and addictive processes and proinflammatory cytokines regulate
Mu Opioid Receptor (MOR) expression. We show
how microglial activation, neuroinflammation and
MORs levels variates during the abstinence andthe relapse phases in female rats and we assess
the role that pain plays on it.

Day 2 • July 23rd
Session #3, Talk #5

Day 2 • July 23rd
Session #4, Talk #1

Pain – Analgesia

Reward – Addiction

11: 4 0 a m – 11: 5 0 a m

11: 5 0 a m – 12 : 0 0 p m

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Eden Anderson

Gregory Grecco

Eden Anderson*, Annabel Engelhardt, Skyler
Demis, Elissa Porath, Matthew Hearing

Gregory G. Grecco*, Briana Mork, David L.
Haggerty, Kaitlin C. Reeves, Yong Gao, Hunter
Hoffman, Andrea R. Masters, Bryan K. Yamamoto,
Patrick L. Sheets, Brady K. Atwood.

Postdoctoral Researcher

Opioid self-administration induced
sex-specific medial prefrontal cortex
plasticity and deficits in cognitive
flexibility
Women transition to addiction faster and experience greater difficulties remaining abstinent,
however what drives this is unknown. We showthat self-administration of the opioid, remifentanil, causes a long-lasting decrease in ex vivo
excitability but augments firing capacity of pyramidal neurons in the prelimbic cortex of mice.
This phenomenon occurs faster in females, manifests from sex-specific changes in excitatory andinhibitory synaptic regulation and aligns with asignificant impairment in cognitive flexibility thatcan be induced and rescued using chemogenetic
manipulations.

M.D-Ph.D. Student

Prenatal Methadone Exposure Disrupts Neurobehavioral Development
We have recently developed and characterized atranslational mouse model of prenatal methadone
exposure (PME) that resembles the typical pattern of opioid use in a pregnant woman who is first
dependent on oxycodone prior to gestation, thenenters a methadone maintenance therapy program, and subsequently becomes pregnant while
maintained on methadone. Using this model, theimpact of PME on behavioral development andneuronal properties using brain slice electrophysiological measures was investigated in offspring.
Methadone was found to accumulate in the fetalcompartment relative to maternal concentrations. In addition to high methadone concentrations in the fetal brain, PME produces substantial
impairments in behavioral development specifically in sensorimotor and locomotor performance
which was associated with alterations in motor
cortical neuron intrinsic properties and synaptic
connectivity.

Day 2 • July 23rd
Session #4, Talk #2

Day 2 • July 23rd
Session #4, Talk #3

Reward – Addiction

Reward – Addiction

12 : 0 0 p m – 12 :10 p m

12 :10 p m – 12 : 2 0 p m

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Lani Tieu

David Reiner

Lani Tieu*, Lauren Smith, Giordano de Guglielmo,
Marsida Kallupi, Olivier George

David J Reiner*, Olivia M Lofaro, Sarah V Applebey,
Hannah Korah, Marco Venniro, Carlo Cifani,Jennifer M Bossert, Yavin Shaham

Research AssistantIdentification of Individual Differences in Response to Methadone,
Buprenorphine, and Naltrexone in an
Animal Model of Opioid Use Disorder
The current medications for opioid use disorder(buprenorphine, methadone, and naltrexone) significantly reduce craving but there are substantial individual differences in response to thesetreatments, and the reason for such difference ispoorly known. Here, we tested the hypothesis thatsimilar individual differences may be observed ina large population of heterogeneous stock rats,that have been bred to maximize genetic diversity,using a behavioral paradigm relevant to opioid use
disorder. We found that ~65% of rats decreased
their motivation to take oxycodone with at least
one treatment and observed large individual difference for each treatment. To unveil the genetic,
cellular, and molecular basis of these differences,
we created the Oxycodone Biobank (www.oxycodonebiobank.org), from which investigators canrequest biological samples, including blood, urine,
feces, brain, liver, kidney, and other organs.

Postdoctoral Researcher

Role of projections between piriform
and orbitofrontal cortex in relapse tofentanyl seeking after food choice-induced voluntary abstinence
There are few preclinical studies of fentanyl
relapse, and these studies have used experimenter-imposed (forced) abstinence procedures,
despite that in humans, abstinence is often voluntary, with drug available in the drug environment but forgone in favor of non-drug alternative
rewards. Using immunohistochemistry, anatomical tracing, and classical pharmacology, I identified a critical role of projections between piriform
and orbitofrontal cortices in relapse to fentanyl
seeking after food choice-induced voluntary
abstinence in both male and female rats. These
data revealed a surprising finding, that the piriform cortex which is traditionally thought of as an
olfaction-related region and not previously studied in the context of drug reinstatement/relapse,
is critical for relapse to fentanyl seeking.

Day 2 • July 23rd
Session #4, Talk #4

Day 2 • July 23rd
Session #4, Talk #5

Reward – Addiction

Reward – Addiction

12 : 2 0 p m – 12 : 3 0 p m

12 : 3 0 p m – 12 : 4 0 p m

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• Back to scheduleDarrell EacretMarwa Mikati

Darrell Eacret*, Polina Fenik, Guanxia Zhan, Sigrid
C. Veasey, and Julie A. Blendy

Marwa Mikati*, Kia Barclay, Petra ErdmannGilmore, Robert Sprung, Reid Townsend, Ream
Al-Hasani

Research Assistant

Ph.D. Candidate

Investigations into the behavioral andmolecular consequences of chronic
opioids and the relationship to disrupted sleep

In vivo detection of endogenous opioid peptides and their role in opioid
withdrawal syndrome

Disrupted sleep is a side effect of opioid use andwithdrawal. We used an oral morphine administration paradigm and found significant alterations
in sleep parameters during morphine exposure
and withdrawal. Increases in wakefulness duringmorphine accompanied a cortical gene expression profile that is reminiscent of an inflammatory sleep deprivation state. Ongoing studies arefocused on identifying molecular mechanisms
underlying these changes and how to intervenewith treatments during withdrawal to improve
sleep disturbances and reduce withdrawal
symptoms.

The withdrawal syndrome associated with abstinence from opioids often results in relapse, issometimes fatal and prevents long-term abstinence. Studies have shown that increased expression of dynorphin mRNA, the endogenous kappa
opioid receptor ligand, increases in the nucleus
accumbens during withdrawal. However, there is
not a reliable method to directly measure in vivochanges in opioid peptides. Here, we propose anovel mouse model of precipitated withdrawal
from chronic fentanyl exposure. We also describe
a method coupling microdialysis and nano-liquid
chromatography/mass spectrometry to allow
detection of endogenous opioid peptides in vivo.

Day 2 • July 23rd
Session #4, Talk #6

Day 2 • July 23rd
Session #4, Talk #7

Reward – Addiction

Reward – Addiction

12 : 4 0 p m – 12 : 5 0 p m

12 : 5 0 p m – 1: 0 0 p m

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Round Table
Academic and Industry Career
Moderators:
Andrea Bedini

Assistant professor, University of Bologna

Lucia Hipolito
Associate professor, University of Valencia

Ream Al-Hasani
Assistant professor, St Louis College of Pharmacy

Jose Moron-Concepcion
Professor, Washington University in St. Louis

Amynah Pradhan
Associate Professor, University of Illinois in Chicago

John Streicher
Assistant professor, University of Arizona

Katherine Martucci
Assistant professor, Duke University

Day 2 • July 23rd–

Round Table
1: 0 0 p m – 2 : 0 0 p m

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• Back to scheduleDay 3 • July 24th

Talks Session #5
11: 0 0 a m – 12 : 2 0 p m

Kappa

Moderators:

Ream Al-Hasani
Lee-Yuan Liu-Chen

Speakers:
11: 0 0 a m – 11:10 a m

Manish K. Madasu
Activation of kappa opioid receptor potentiates cold
sensation
11:10 a m – 11: 2 0 a m

Michelle Morochnick
Modulation of cocaine administration by kappa agonists:
nalfurafine and novel pyranopiperazines

receptors (KOR)-inducible Cre recombinase (KOR-iCre),a better tool for precise localization of KOR-expressing
neurons
12 : 0 0 p m – 12 :10 p mMoriah L. Jacobson
Kappa Opioid Receptor Desensitization is Required for theProtracted Antidepressant Effects of Ketamine
12 :10 p m – 12 : 2 0 p m

Valentina Martinez DamontekORs in the VTA modulate GABAergic synaptic plasticity

Talks Session #6
12 : 2 0 p m – 1: 4 0 p m

Pain

Moderators:

Catherine Cahill
Nicolas Massaly

11: 2 0 a m – 11: 3 0 a m

Alexander French
Effects of biased agonism at the kappa opioid receptor
on alcohol consumption in mice
11: 3 0 a m – 11: 4 0 a m

Sarah C. Simmons
Early life stress dysregulates kappa opioid receptor signaling within the lateral habenula
11: 4 0 a m – 11: 5 0 a m

Susan Ahmedyar
The role of dynorphin/kappa-opioid receptor (DYN-KOR)
system in stress-mediated affective disorders and alcohol self-administration in mice
11: 5 0 a m – 12 : 0 0 p m

Danni Cao
Characterization of knockin mice harboring kappa opioid

Speakers:
12 : 2 0 p m – 12 : 3 0 p m

Courtney A. Bouchet
Differential effects of persistent inflammation on the presynaptic opioid and cannabinoid receptors within the ventrolateral periaqueductal gray
12 : 3 0 p m – 12 : 4 0 p m

Bryan Sears
Potential Involvement of Peripheral Opioid Receptors In
The Development Of Tolerance To Morphine
12 : 4 0 p m – 12 : 5 0 p m

Zachariah Bertels
A translationally significant model of migraine facilitation
through chronic morphine is attenuated by PAC1 receptor
antagonism

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12 : 5 0 p m – 1: 0 0 p m

Evan F. Fullerton
The impact of advanced age on Mu Opioid Receptor signaling in the midbrain periaqueductal gray: implications
on analgesia
1: 0 0 p m – 1:10 p m

Benjamin M. Clements
Influence of Strategically Substituted Agmatines on
Opioid-Induced Neuroplasticity
1:10 p m – 1: 2 0 p m

Sarah Palumbo
Assessment of probable opioid use disorder using electronic health record documentation
1: 2 0 p m – 1: 3 0 p m

Tamara Markovic
Pain induces somatic adaptations in Ventral Tegmental
Area Dopamine neurons to drive anhedonia-like behavior
1: 3 0 p m – 1: 4 0 p m

Kylie B. McPherson
Changes in intrinsic properties of vlPAG neuron subtype
after persistent inflammatory pain

Conclusion and Valencia
Meeting presentation
1: 4 0 p m – 2 : 0 0 p m

Speakers :Larry Toll
Nicolas Massaly
Lucia Hipolito

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Manish K. Madasu

Michelle Morochnik

Manish K. Madasu*, Loc V. Thang, Priyanka
Chilukuri, Sasha Singh, Tayler D. Sheahan, Jordan
G. McCall, Ream Al-Hasani

Michelle Morochnik*, Kyle Windisch, Amelia Dunn,
Philip Pikus, Ariel Ben-Ezra, Brian Reed, Mary
Jeanne Kreek

Activation of kappa opioid receptor
potentiates cold sensation

Modulation of cocaine administration
by kappa agonists: nalfurafine andnovel pyranopiperazines

Postdoctoral Researcher

Noxious cold sensation is commonly associatedwith peripheral neuropathies, however there has
been limited progress in understanding the mechanism of cold pain. Here we investigate the roleof kappa opioid receptor (KOR) in mediating cold
sensation. Wildtype mice (WT) injected with
U50,488 (U50) (KOR agonist, 5mg/kg i.p) show
significant potentiation in the number of jumps
on the cold plate compared to controls at 3ºC
and NorBNI (KOR antagonist) blocked the U50induced nocifensive responses. Peripheral novel
agonist CR845 had a similar effect to U50 on thecold plate. U50 or CR845 had no effect on rectal
body temperature vs control, suggesting no roleof central thermoregulation. Together, these findings identify a novel role for the peripheral kappa
opioid receptor system in the potentiation of cold
sensation.

Research AssistantIn progressive ratio studies in C57BL/6 mice nalfurafine causes an increase in progressive ratio
breakpoint during cocaine self-administration.
In two novel kappa opioid receptor agonists, wefound one had no effect and the other had a trend
toward reduction of progressive ratio breakpoint.

Day 3 • July 24th
Session #5, Talk #1

Day 3 • July 24th
Session #5, Talk #2

Kappa

Kappa

11: 0 0 a m – 11:10 a m

11:10 a m – 11: 2 0 a m

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Alexander French

Sarah C. Simmons

Alexander R. French*, Q. Hawk Royer, Anna M.
Gutridge and Richard M. van Rijn

Sarah C. Simmons*, Ryan D. Shepard, Shawn
Gouty, Ludovic D. Langlois, Brian M. Cox andFereshteh S. Nugent

Postdoctoral Researcher

Effects of biased agonism at the
kappa opioid receptor on alcohol
consumption in mice
The roles of kappa opioid receptor (KOR) signaling in regulating stress and reward make it an
attractive target for treating alcohol use disorder(AUD), but this approach is limited by the dysphoric and sedative side effects of KOR activation. Different signaling pathways downstreamof the KOR have been associated with different
physiological outcomes, driving the development of “biased” agonists that preferentially signal through one pathway or another. This study
examines the potential of biased agonism to treat
AUD by correlating the pharmacological bias ofdifferent KOR-specific ligands with their effects
on voluntary ethanol consumption in mice using
a two bottle choice drinking paradigm.

Postdoctoral Researcher

Early life stress dysregulates kappa
opioid receptor signaling within thelateral habenula
While there is evidence for direct dynorphin/kappa opioid receptor (DYN/KOR) regulationof the mesocorticolimbic system, to date there
has been little study on KOR regulation of otherimportant stress/mood-related regions such as
the lateral habenula (LHb). Here we provide significant evidence for the presence of a functional
DYN/KOR modulation of LHb activity through both
intrinsic properties and synaptic modulation indiscrete populations of LHb neurons identified by
the presence of the hyperpolarization-activatedcurrent (Ih). Secondly, we found that severe earlylife stress dysregulated DYN/KOR signaling downstream from receptor signaling which resulted inblunted responses of LHb neurons to acute KOR
stimulation. To our knowledge, this is the firststudy directly assessing the effects of DYN/KOR
signaling on LHb neuronal excitability, and providing evidence for DYN/KOR dysregulation in the
LHb following severe early life stress.

Day 3 • July 24th
Session #5, Talk #3

Day 3 • July 24th
Session #5, Talk #4

Kappa

Kappa

11: 2 0 a m – 11: 3 0 a m

11: 3 0 a m – 11: 4 0 a m

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• Back to scheduleSusan Ahmedyar

Danni Cao

Susan Ahmedyar*, Kabirullah Lutfy

Chongguang Chen, Danni Cao*, Lan Hsuan Melody
Huang, Lee-Yuan Liu-Chen

M.S. Candidate

The role of dynorphin/kappa-opioid
receptor (DYN-KOR) system instress-mediated affective disorders
and alcohol self-administration inmice
In a preliminary study, we evaluated the impact ofage and the role of DYN-KOR system in the development of negative affective states that occur following repeated variable stress exposure as wellas in alcohol self-administration in female mice.
Preprodynorphin null mice and their littermates/
controls underwent a 10-day repeated variable
stress exposure followed by alcohol self-administration in the home cage. Our results revealed
that endogenous dynorphin plays a significant
role in the development of depression-like behavior and alcohol self-administration in an age-related manner.

Postdoctoral Researcher

Characterization of knockin miceharboring kappa opioid receptors(KOR)-inducible Cre recombinase(KOR-iCre), a better tool for precise
localization of KOR-expressing neurons
We generated a knockin mouse line expressing an
inducible Cre in the oprk1 gene (KOR-iCre), crossbred with Ai6 mice and induced with tamoxifen
in adulthood to enable expression of ZsGreen incytosol of KOR cells. Three-dimensional images of
CLARITY-cleared brains will be presented, whichdisplay high density of KOR-expressing cells
in the claustrum, dorsal endopiriform nucleus,
basolateral amygdala, prefrontal cortex, nucleus
accumbens, substantia innominata and nucleus
reunion, similar to distribution of KOR mRNA. The
mouse line also facilitates precise identificationof KOR-expressing cells at the cellular level. This
KOR-iCre line is different from the previous KORCre mouse line of S. Ross’ lab., in which Cre isexpressed constitutively in KOR cells and thus in
all KOR-lineage cells, not just those expressing
KOR in adulthood. This mouse line will be a valuable tool for investigation of KOR.

Day 3 • July 24th
Session #5, Talk #5

Day 3 • July 24th
Session #5, Talk #6

Kappa

Kappa

11: 4 0 a m – 11: 5 0 a m

11: 5 0 a m – 12 : 0 0 p m

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Moriah L. Jacobson

Valentina Martinez Damonte

Moriah L. Jacobson*, Sarah C. Simmons,Hildegard A. Wulf, Fereshteh S. Nugent, Caroline
A. Browne, Irwin Lucki

Valentina Martinez Damonte*, Julie Kauer

Postdoctoral Researcher

Kappa Opioid Receptor Desensitization is Required for the Protracted
Antidepressant Effects of Ketamine
We hypothesized that the kappa opioid receptor (KOR) system is necessary for ketamine toexert its rapid and sustained antidepressantactivity. Our data demonstrate that 1) ketamine
pretreatment prevents behavioral and electrophysiological responses caused by subsequent
KOR activation, and 2) these responses in miceare prevented by prior KOR blockade. These studies provide evidence that ketamine reduces KOR
signaling which may contribute to the protracted
clinical antidepressant effects of ketamine.

Postdoctoral Researcher

kORs in the VTA modulate GABAergic synaptic plasticity
We have previously identified kORs as key players
in stress-induced alterations in VTA synaptic plasticity since a single acute exposure to cold-water
swim stress blocks a form of potentiation of inhibitory postsynaptic currents (LTPGABA) on VTA
dopaminergic cells due to a persistent, ligand-independent constitutive activation of kappa opioid
receptors.
Both dopaminergic and non-dopaminergic cells inthe VTA receive dynorphin inputs from different
brain regions. Here, using a conditional knock out
approach we selectively deleted kORs in dopaminergic neurons and found that this deletion did
not prevent stress-induced block of LTPGABA. We
have also begun to identify the specific GABAergic
pathways to the VTA that exhibit this form of
LTPGABA using optogenetics.
Our work contributes to the understanding of theeffects of endogenous opioids within the VTA aswell as the relevance of GABAergic modulationof the reward pathways.

Day 3 • July 24th
Session #5, Talk #7

Day 3 • July 24th
Session #5, Talk #8

Kappa

Kappa

12 : 0 0 p m – 12 :10 p m

12 :10 p m – 12 : 2 0 p m

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Courtney A. Bouchet

Bryan Sears

Courtney A. Bouchet*, Katherine L. Suchland,
Susan L. Ingram

Bryan Sears*, Emily Jutkiewicz

Graduate Student

Differential effects of persistent
inflammation on the presynaptic opioid and cannabinoid receptors within
the ventrolateral periaqueductal gray
Opioids and cannabinoids are both used to treat
pain; however, it is not well understand whether
these systems function differently after pain. In
these experiments, we use slice electrophysiology to determine functional changes in the presynaptic opioid and cannabinoid systems in theventrolateral periaqueductal gray, a region of thedescending pain modulatory pathway, after persistent inflammation in male and female Sprague
Dawley rats. We find that persistent inflammation
does not appear to effect the function of the presynaptic mu opioid receptor but induces plasticity
in the cannabinoid system, reducing the functionof the cannabinoid 1 receptor.

Graduate Student

Potential Involvement of Peripheral
Opioid Receptors In The Development Of Tolerance To Morphine
Tolerance plagues the use of opioid analgesics
but the mechanisms of tolerance are not fully
understood. Here, we show the activation of opioid
receptors in the peripheral nervous system is sufficient for inducing tolerance to the antinociceptive effects of morphine. Further, antagonism of
peripheral opioid receptors with naloxone-methiodide attenuates the development of tolerance,suggesting the involvement of peripheral opioid
receptors in tolerance development.

Day 3 • July 24th
Session #6, Talk #1

Day 3 • July 24th
Session #6, Talk #2

Pain

Pain

12 : 2 0 p m – 12 : 3 0 p m

12 : 3 0 p m – 12 : 4 0 p m

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Zachariah Bertels

Evan F. Fullerton

Zachariah Bertels*, Kendra Siegersma, Serapio
M. Baca, Amynah Pradhan

Evan F. Fullerton*, Myurajan Rubaharan, Mary C.
Karom, and Anne Z. Murphy, PhD

A translationally significant model ofmigraine facilitation through chronicmorphine is attenuated by PAC1
receptor antagonism

The impact of advanced age on Mu
Opioid Receptor signaling in the
midbrain periaqueductal gray: implications on analgesia

Migraine is an extremely common and debilitating
disorder, which can be worsened through continued treatment with mu-opioid receptor agonists.
Here we translated this phenomenon, in mice, in
two mechanistically distinct models of migraine
such that, repeated morphine treatment resulted
in exacerbation of migraine correlates. Further,
we found that this exacerbation of migraine could
be reversed through antagonism of the primary
PACAP receptor, PAC1, demonstrating the effectiveness of our model to not only translate aknown human phenomenon, but also to successfully screen potential new therapeutic targets.

Chronic pain is exceedingly prevalent in individuals over 65 years of age, but is under-managed
in this population. We used cellular and pharmacological techniques to assess age-induced
alterations in opioid binding and signaling in the
midbrain ventrolateral periaqueductal gray of therat, a critical region in the modulation of pain. Our
novel findings elucidate the mechanisms responsible for reduced morphine potency in aged animals and identify potential therapeutic targets toimprove pain management in the elderly.

Graduate Student

Graduate Student

Day 3 • July 24th
Session #6, Talk #3

Day 3 • July 24th
Session #6, Talk #4

Pain

Pain

12 : 4 0 p m – 12 : 5 0 p m

12 : 5 0 p m – 1: 0 0 p m

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• Back to schedule

Benjamin M. Clements

Sarah Palumbo

BM Clements*, CD Peterson, KF Kitto, GL Wilcox,
and CF Fairbanks

Sarah A. Palumbo*, Kayleigh M. Adamson,
Sarathbabu Krishnamurthy, Shivani Manoharan,
Donielle Beiler, Anthony Seiwell, Colt Young, Raghu
Metpally, Richard C. Crist, Glenn A. Doyle, Thomas
N. Ferraro, Mingyao Li, Wade H. Berrettini, Janet
D. Robishaw, Vanessa Troiani

Graduate Student

Influence of Strategically Substituted
Agmatines on Opioid-Induced Neuroplasticity
Agmatine, an putative neurotransmitter, hasbeen shown to reduce the negative side effects
of opioids while enhancing opioid analgesia after
exogenous administration. Due to a non-ideal
CNS distribution and pharmacokinetic profile,
we have developed a series of strategically substituted agmatines, designed for increased lipophilicity and brain penetration while maintaining
the pharmacologic activity of agmatine. These
strategically substituted agmatines prevent thedevelopment of chronic morphine tolerance after
intrathecal and subcutaneous administration.

Second Year Medical Student

Assessment of probable opioid use
disorder using electronic healthrecord documentation
In this retrospective, cross-sectional study, wedemonstrated that a series of proxy measures foreach of the DSM-5 criteria for Opioid Use Disorder(OUD) can be extracted through Electronic Health
Record (EHR) review and further demonstrated
increases in OUD prevalence and psychiatriccomorbidities in patients that are part of a drug
monitoring program. The use of proxy measuresthat rely on multiple sources of data, including
prescription drug history and medical record
notes, can help to identify patients with OUD thathave not been diagnosed, as OUD is traditionally
underdiagnosed from an analysis of ICD Codes.
The development and implementation of precision medicine approaches could become a major
factor in developing more efficient and personalized pain treatments with less risk for addiction,
for which studies of this potential could be helped
by establishing more effective proxy measures for
OUD using EHR data.

Day 3 • July 24th
Session #6, Talk #5

Day 3 • July 24th
Session #6, Talk #6

Pain

Pain

1: 0 0 p m – 1:10 p m

1:10 p m – 1: 2 0 p m

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• Back to schedule

Tamara Markovic

Kylie B. McPherson

Tamara Markovic*, Nicolas Massaly, ChristianPedersen, Kavitha Abiraman, Jung Hoon Shin,
Brian Ruyle, Yvan Vachez, Jeniffer Garcia, Veronica
A. Alvarez, Michael R. Bruchas, Meaghan Creedand Jose A. Morón

Kylie B. McPherson*, Courtney A. Bouchet, andSusan L. Ingram

Ph.D. Student

Pain induces somatic adaptations in
Ventral Tegmental Area Dopamine
neurons to drive anhedonia-likebehavior
Pain is a complex phenomenon composed of sensory and negative affective component, whose
common characteristic is a decrease in motivation to initiate and complete goal-directed behavior. Using chemogenetics, fiber photometry, slice
electrophysiology and voltammetry we found thatpain decreases the activity of mesolimbic VTA
DA neurons concurrent with reduced motivation
for natural rewards which can be overcome by
selective activation of VTA DA neurons, decreases
spontaneous firing and intrinsic excitability of VTA
DA neurons and leads to dysregulation of MOR
system in the VTA. In conclusion, our findings
reveal that somatic adaptations within VTA DA
neurons underlie pain induced negative affect.

Ph.D. Candidate

Changes in intrinsic properties ofvlPAG neuron subtype after persistent inflammatory pain
Electrophysiological characterization of the vlPAG
uncovered 4 cell types with distinct firing patterns. One of these 4 types exhibited enhanced
basal activity after persistent inflammatory pain.
Future directions will investigate the potential roleof excitatory afferents in this enhanced activity
as well as the presence of any alterations to synaptic machinery.

Day 3 • July 24th
Session #6, Talk #7

Day 3 • July 24th
Session #6, Talk #8

Pain

Pain

1: 2 0 p m – 1: 3 0 p m

1: 3 0 p m – 1: 4 0 p m

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SponsorsThank You to our Generous
Sponsors!

IT support by
Washington University in St. Louis

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INRC 2020
Committees
INRC Officers

INRC Executive Committee

Larry Toll

Ream Al-Hasani
Emily Jutkiewicz
Brian Reed
Stefan Schulz
Andrea Bedini
Eamon Kelly
Minoru Narita
Shogo Tokuyama
Jing Gen Liu(President, USA)

Lee Yuan Liu-Chen(Treasurer, USA)

Amynah Pradhan(Information Officer, USA)

Organizing Committee
Nicolas Massaly
Lucia Hipolito
Ream Al-Hasani
Jose Moron-Concepcion
Amynah Pradhan
Emily Jutkiewicz
Andrea Bedini
Brian Reed
Eamonn Kelly
Larry Toll
Lee Yuan Liu-Chen

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ADVANCES IN OPIOID“NEWRESEARCH: FROM BENCH
TO THE BEDSIDE
”

INRC
2020
21

See you in Valencia!
VALENCIA (SPAIN)
~July
6-10
July2021
2020 | Hotel Meliá Valencia

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