Oral Presentation The International Congress of Neuroendocrinology 2014

Pharmacological Enhancement of Social Behaviour: Party Drugs, Neuropeptides and Novel Therapeutics (#35)

Iain S McGregor 1
  1. School of Psychology, The University of Sydney, Sydney , NSW, 2006, Australia

Many psychiatric disorders involve a primary or secondary disturbance in social functioning. Obvious examples include autism and social anxiety disorder, with social deficits also commonly observed in major depressive disorder, schizophrenia and addictions. Targeted pharmacological enhancement of social cognition and social behavior is a potentially useful therapeutic strategy. Rodent models such as the social interaction, social preference and social conditioned place preference tests can identify compounds with prosocial effects. Our own research initially focused on the drug MDMA (‘Ecstasy’) which has powerful empathogenic effects in humans. MDMA profoundly increases social interaction in rats meeting for the first time, causing prolonged bouts of passive social contact called “adjacent lying”. These effects are mimicked by peripheral injections of oxytocin (OT, 0.5 mg/kg) or vasopressin (AVP, 0.01 mg/kg) and are prevented by the vasopressin V1A receptor antagonist SR49059 (1 mg/kg). MDMA, OT and AVP also increase the time spent with a conspecific relative to an inanimate object (social preference), and both MDMA and OT also confer a strong preference for a context in which social interaction has taken place (social place preference). Due to possible neurotoxicity (MDMA), autonomic side effects (AVP), or limited brain penetration (OT/AVP) it is unlikely that MDMA, OT or AVP will ultimately provide a convincing clinical intervention. The non-peptide oxytocin receptor (OTR) agonist WAY 267,464 has attracted substantial recent interest as an alternative. However, we have found limited efficacy of WAY 267,464 in social paradigms with rodents, and that it has powerful V1A antagonist effects additional to its OTR agonist action. Another small molecule compound, SOC-1, which is an indirect modulator of brain OT systems, provides a powerful and long-lasting enhancement of social behavior in rodent models. Recent encouraging results with this compound will be discussed.