STEREOSPECIFIC EFFECTS OF MDMA ON OXYTOCIN ACTIVITY AND OXYTOCIN-DEPENDENT BEHAVIOR

3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive drug that has many observable pro-social effects and potentially therapeutic effects, including increased sociability, increased empathy, and facilitation of fear extinction. It is currently under investigation as a treatment for PTSD and autism. Previous studies have reported that MDMA increases release of the neuropeptide oxytocin, a critical regulator of many social behaviors. Its release has been proposed as a mechanism for the pro-social effects of MDMA. MDMA is a racemic mixture of two enantiomers, S+ and R-, that have distinct physiological and behavioral effects. We hypothesize that some of these differences may be due to stereospecific activation of oxytocin.To determine if differential activation of oxytocin neurons might account for the distinct prosocial effects of MDMA’s enantiomers, we used immunofluorescence to quantify cFos-active oxytocin neurons in the paraventricular nucleus (PVN) following treatment with MDMA and its enantiomers in mice. To determine if oxytocin was necessary for observed prosocial behavioral effects, we administered a selective oxytocin antagonist before treatment with MDMA and, later, a subsequent social interaction test. The durations of three social behaviors were scored: anogenital investigation, general investigation, and adjacent lying. MDMA and both of its enantiomers significantly increased cFos expression in oxytocin containing neurons of the PVN. In the social behavior test, oxytocin antagonist attenuated adjacent lying behavior, but had no effect on general or anogenital investigation. The results suggest that oxytocin may be necessary for MDMA induced adjacent lying behavior but not other social behaviors. Furthermore, it is unlikely that differential release of oxytocin accounts for the distinct behavioral effects of MDMA’s enantiomers. Therefore, while oxytocin may be an important mediator of MDMA’s effects, these data indicate that it is not necessary for all MDMA-induced social behaviors and is not sufficient for the therapeutic-like effects of MDMA. Since MDMA and its enantiomers show tremendous promise as a treatment for behavioral disorders, it is important to understand the pharmacological mechanisms underlying its behavioral effects.