Disruption of cortical N-methyl-d-aspartate receptor tone governs impulsive action

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e119 Disruption of cortical N-methyl-d-aspartate receptor tone governs impulsive action Christopher Krebs, Noelle C. Anastasio, Charity Wood Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States Aims: Impulsivity is a complex, multifaceted trait broadly defined as actionwithout sufficient foresight; high inherent impulsive action may increase the likelihood that drug use escalates into dependence and relapse. Glutamate neurotransmission within the medial prefrontal cortex (mPFC) may critically regulate the cognitive and/or behavioral dimensions underlying impulsive action.We tested the hypothesis that disruption in NMDAR expression within the mPFC drives inherent impulsive action, and that pharmacological potentiation of NMDAR attenuates high inherent impulsive action. Methods: A one-choice serial reaction time (1-CSRT) task was used to identify outbred male Sprague Dawley rats with high (HI) or low (LI) inherent impulsive action. Rats nose-poked for food pellets. Premature responses indexed impulsivity; the upper and lower 25% of rats were identified as HI or LI rats, respectively. Rats from one cohort were sacrificed andmPFC synaptosomal protein extracted; western blots were used to assess NMDAR subunit expression. Effects of saline (1ml/kg, ip) ord-cycloserine (DCS, agonist at strychnine-insensitive glycine site of NMDAR; 20mg/kg, ip) on impulsive action were assessed in a separate cohort of HI and LI rats. Results: Performance on the 1-CSRT task was rapidly acquired and allowed stable identification of HI and LI rats across 70 training days (p<0.001). HI rats had lower mPFC GluN1 and GluN2A synaptosomal protein expression compared to LI rats (p<0.05). Differences in GluN2B expression between HI and LI rats were not detected. DCS decreased impulsive action in HI, but not LI, rats (p=0.05). Conclusions: Diminished mPFC GluN1/GluN2A signaling may drive high inherent impulsive action, which can be rescued by selective potentiation of NMDAR function. Increased understanding of the neurobiology underlying inherent differences in impulsive action may aid development of pharmacotherapies targeting drug dependence, relapse, and other disorders characterized by aberrant impulsivity. Financial support: NIH K99 DA033374. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.328 The cost-effectiveness of opioid agonist treatment in California’s publicly-funded drug treatment facilities Emanuel Krebs1, Libo Li2, Jeong Eun Min1, Elizabeth Evans2, R. Rawson2, Yih-Ing Hser2, Bohdan Nosyk1 1 BC Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada 2 UCLA Integrated Substance Abuse Programs, Los Angeles, CA, United States Aims: California treats the largest population of opioid dependent individuals in the USA. We assessed the cost-effectiveness of the current standard of OAT in California, compared to a scenario in which all entrants access non-time-limited (or maintenanceoriented) OAT. Methods: We adapted a previously published semi-Markov cohort model to capture the chronic, recurrent nature of opioid dependence. We used linked state-wide administrative data on drug treatment and incarceration, supplemented with other published data, to populate our model, which distinguishes between prescription opioid (PO) and heroin users. We compared an ‘actual practice’ scenario based on the observed distribution of PO and heroin users across detoxification and maintenance at first treatment to the hypothetical scenario of all treatment entrants initiating maintenance. Calculations were done over 1, 5, 10-year and lifetime horizons. Results:Allowing all treatment entrants to have access tomaintenance treatment at first treatment episode was found to be a dominant strategy in each of the time horizons, resulting in lower total costs and higher quality-adjusted life-year (QALY) gains. Over a lifetime horizon, our model showed that people who initiated maintenance upon first treatment entry gained 13.0 discounted QALYs on average (vs 12.1 for those receiving the standard of care) and generated a societal cost of $0.74 million (vs $1.02 million). Cost savings were realized primarily because of treatment retention and the lower costs of criminality associated with the reduced time spent out-of-treatment. Conclusions: Synthesizing population-level data on OAT in publicly-funded drug treatment facilities in California, we found that immediate access to maintenance treatment may be more effective and less costly than the current standard of care for people with chronic opioid dependence. Financial support: NIDA R01DA031727 (PI:Nosyk) R01 DA032551 (PI:Nosyk) P30DA016383 (PI:Hser). http://dx.doi.org/10.1016/j.drugalcdep.2015.07.329 Predictors of e-cigarette use among adolescents S. Krishnan-Sarin2, Grace Kong2, Deepa R. Camenga1, Dana A. Cavallo2, Patricia Simon2, Christian Connell 2, Ran Wu2, Meghan E. Morean2 1 Pediatrics, Yale School of Medicine, New Haven, CT, United States 2 Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States Aims: To develop an understanding of perceptions, use patterns and predictors of e-cigarette use among adolescents. Methods: Surveys conducted in CT middle schools (MS) and high schools (HS) in November, 2013 (Time 1; n=4780) and June 2014 (Time 2; n=5012). Results: Cross-sectional analyses at Time 1 indicated high rates of lifetime use (3.5% MS, 25.4% HS) and current (past month) use (1.5% MS, 12% HS) of e-cigarettes and these rates increased further at Time 2 (lifetime use: 7.4% MS, 28% HS; past month use: 3.7% MS, 12% HS). At Time 1, males (OR=1.70, p<0.01), older students (OR=1.39, p<0.05), Caucasians (OR=2.01, p<0.001), students who had tried cigarettes but were not current cigarette smokers (ever smokers; OR=13.04, p<0.001), and current cigarette smokers (OR=65.11, p<0.001) were more likely to be lifetime e-cigarette users, and report greater susceptibility to future e-cigarette use (Males: OR=1.30; Caucasians: OR=1.14; ever cigarette smokers; OR=3.85; current cigarette smokers; OR=9.81; ps <0.01). Longitudinal examinations with students surveyed at both time-points (n=2090) observed that among those who were never e-cigarette users (n=1750) at Time 1, adolescentswhowere older (OR= =1.24, p< .0001) and lifetime cigarettes users (OR=2.93, p=0.009), and who did not think that e-cigarettes were harmful (OR=0.47, p< .0001) and thought that e-cigarettes were safer than regular cigarettes (OR=2.11, p=0.0003), and who were susceptible to