Oxytocinergic regulation of endogenous as well as drug-induced mood

Abstract

The interconnections between the serotonin and oxytocin pathways in the brain suggest that changes in oxytocin levels - arising from natural or drug-induced stimuli - lead to measureable changes in mood. In this paper, we review our findings in the context of what is known about the roles of oxytocin and vasopressin in the expression of a range of behaviours. In our first set of studies we investigated whether stimulation of oxytocin and vasopressin receptors, via central or systemic drug administration, would produce behavioural changes indicative of anti-depressant or anxiolytic activity. In our second study we investigated whether oxytocin receptor activation might be implicated in the interoceptive effects experienced with the popular party drug, MDMA (‘ecstasy’). Our first study demonstrated that carbetocin, an oxytocin analogue, had anti-depressant actions following systemic and central administration, effects which were blocked by the oxytocin and vasopressin 1A receptor antagonist, atosiban. Carbetocin also had anxiolytic effects in the elevated plus maze. In an evaluation of the complementary nature of oxytocin and vasopressin, we found that systemic administration of desmopressin, a vasopressin analogue, was anxiogenic; its effects blocked by atosiban which on its own produced robust anxiolytic behavioural changes. In our second study, we evaluated MDMA’s interoceptive effects using a drug discrimination paradigm. Carbetocin partially substituted for MDMA, while atosiban interfered with MDMA discrimination, suggesting that oxytocin receptor activation contributes to MDMA-related interoceptive cues. The results of these and other clinical and preclinical studies suggest that oxytocin, as well as its closely related counterpart vasopressin, may provide alternative therapeutic targets for the treatment of mood disorders such as anxiety and depression. The possibility that oxytocin release may contribute to the perception of and processes underlying natural and drug-induced behavioural reinforcement offers exciting prospects for future study.