Dissecting the Role of Estradiol in Mediating Gender-specific Anxiolytic and Prosocial Effects of Oxytocin
Condition: Oxytocin; Estrogen; Fear Extinction; Emotion Processing; Memory
Study type: Interventional
Phase: Phase 1

Summary: 
      The study aims to examine a behavioral and neural framework for understanding the
      sex-specific effects of the neuropeptide oxytocin (OXT). Using hormonal, behavioral and
      neuroimaging readouts, it is planned to explore the interplay of OXT and estradiol as a
      potential mechanism mediating sexual dimorphic effects.
    

Detailed description: 
      The study comprises two subprojects (Study 1 and Study 2). In Study 1, the investigators will
      compare the effects of OXT on fear extinction and fear recall as well as on emotion
      recognition between women and men. Additionally, the investigators plan to test whether a
      pretreatment with exogenous estradiol can be used to augment these OXT effects. In Study 2,
      the investigators will use functional magnetic resonance imaging (fMRI) to elucidate the
      effects of OXT-estradiol interactions on neural responses in an emotional face matching task
      and an emotional memory task. Half of the participants will be included in Study 1 and the
      other half in Study 2.

      Study 1 contains three test sessions (after the screening). In the first session participants
      will complete a fear conditioning paradigm. The second session will take place on the
      following day and will start with the administration of estradiol gel (Divigel; 2 mg) or
      placebo (PLC). Three hours after the gel administration the participants will intranasally
      self-administer 24 IU of OXT or PLC under supervision and 30 min later a fear extinction task
      will commence, followed by an emotion recognition paradigm. A fear extinction recall task
      (identical with the fear conditioning task except for the electric shocks) will be conducted
      in the third session (with a 24-hours break between the second and the third session).

      In Study 2, participants will be randomly assigned to four different treatment conditions (1.
      OXT + PLC gel; 2. OXT + estradiol gel; 3. PLC + PLC gel; 4. PLC + estradiol gel) after the
      screening session. The timing of the drug administration and blood sample collection will be
      identical to that of the second session of Study 1. The fMRI paradigms (resting state,
      emotional face matching and emotional memory) will start 30 minutes after nasal spray
      administration. Three days after the scanning, participants will be tested with a surprise
      recognition task, which includes pictures shown in the scanner and distractors.
    

Intervention name(s): Oxytocin nasal spray; Placebo nasal spray; Estrogen Gel; Placebo Gel
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Intranasal administration of 24 International Units, Oxytocin will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).; The placebo spray contains the identical ingredients, except for the peptide itself. It will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).; Participants received a single dose of estradiol gel (Estramon 2 mg estradiol, Hexal AG, Holzkirchen, Germany), applied to their shoulder, 3 hours prior to the fear extinction task (Study 1) or fMRI measurement (Study 2).; Participants received a single dose of the placebo gel (ultrasonic gel, 2 mg), applied to their shoulder, 3 hours prior to the fear extinction task (Study 1) or fMRI measurement (Study 2).
Intervention MeSH terms: Oxytocin; Estrogens
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: fMRI; Oxytocin; Estrogen; Memory; Emotion Processing