The prosocial effects of oxytocin, vasopressin and 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in laboratory rats

Abstract

Introduction: The neuropeptides oxytocin (OT) and vasopressin (AVP) are well known for their ability to modulate social behaviours in humans and animals. Several studies have suggested a link between psychiatric illnesses characterised by impaired social interactions (e.g. autism), and disrupted function of the OT and/or AVP systems. The party drug 3,4- methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) is known for its capacity to enhance social behaviour. MDMA is also of interest in the clinic as a possible therapeutic for certain disorders (e.g. post-traumatic stress disorder). The therapeutic potential of MDMA and its ability to enhance sociability, may be due to an increase in the release of OT and AVP in the brain. These results suggest that peripherally administered OT and AVP may increase sociability in rats in a manner analogous to MDMA. The present thesis provides a formal comparison of the behavioral effects of OT, AVP and MDMA. Methods: The effects of peripherally administered OT, AVP and MDMA on social behaviour in rats were examined using three different paradigms. Chapter 2 assessed social interaction, Chapter 3 used the social preference test and Chapter 4 investigated their effects in a social conditioned place preference (social-CPP) test. Chapter 5 looked at the social interaction and autonomic effects of intranasal AVP. In addition, the role the oxytocin receptor (OTR) and vasopressin 1A receptor (V1AR) in the social effects of the three drugs was assessed using selective antagonists in Chapters 2 and 3. Results: OT, AVP, MDMA all induced the prosocial behaviour adjacent lying in the social interaction test. These effects were blocked by the V1AR antagonist, SR49059 but not the OTR antagonist, Compound 25 (C25). Results from the social preference test indicated that OT, AVP and MDMA induced a social preference in well-handled rats. C25 blocked OT and AVP-induced social preference, but not the preference produced by MDMA, in well-handled rats. In contrast, rats that received minimal handling displayed a social preference at baseline, while MDMA, OT and AVP reduced investigation times of both stimuli. Findings from the social-CPP test showed that OT and MDMA, but not AVP produced a long lasting place preference when paired with a conspecific or a tennis ball. Lastly, nebulized AVP increased prosocial behavior and decreased body temperature and heart rate. Conclusions: The results from this thesis indicate that while the behavioural effects of OT, AVP and MDMA are superficially similar they differ in important ways and may involve different neural mechanisms. These findings provide limited support for the idea that OT and/or AVP solely mediate the prosocial effects of MDMA.