A neuromodulatory role for oxytocin within the supramammillary nucleus

Oxytocin functions as both a neurohypophysial hormone and central neuromodulatory peptide, and has been implicated in reproductive behaviours, anxiety and reward, as well as facilitation of the neuroendocrine milk-ejection reflex. A potential substrate for oxytocin is the supramammillary nucleus (SuM), a structure that contains oxytocin binding sites and serves as an important relay within the limbic system. Hence, this study investigated the neuromodulatory role of oxytocin within the SuM. Firstly, the effect of oxytocin on neuronal firing within the SuM was studied, using in vitro brain slices from virgin female rats. Oxytocin (10(-6)M) excited approximately 50% of SuM neurones, and similar results were obtained with the selective oxytocin agonist, Thr(4) Gly(7) oxytocin (TGOT) (10(-6) and 10(-7)M). The remaining neurones were unaffected. The TGOT response was blocked by application of the oxytocin antagonist, [d(CH(2))51,Tyr(Me)(2),Thr(4),Orn(8),Tyr-NH29]-vasotocin. Repeat doses of TGOT caused diminution of the response, indicative of desensitisation. In the second series of experiments, immunocytochemical techniques were used to study the oxytocinergic innervation of the SuM. The supramammillary decussation was found to contain numerous oxytocinergic fibres, and some could be seen coursing ventrally to enter the SuM. Whereas, some were clearly "en passant" fibres innervating the neurohypophysis, others followed a more convoluted and branching course, and appeared to terminate within the nucleus. Finally, in vivo microinfusion studies investigated whether oxytocin injected into the SuM facilitated the milk-ejection reflex, a well known action of central oxytocin. Oxytocin microinfusion in the region of the SuM caused a pronounced facilitation of the reflex, contrasting with the much smaller effects of microinfusions made rostral or caudal to the nucleus. Collectively, these results strongly support a neuromodulatory role for oxytocin within the SuM. This could have important implications for understanding the diverse neuroendocrine and behavioural functions of central oxytocin, including its role in reward.