We recently showed that central injections of -melanocyte-stimulating hormone (-MSH) inhibits oxytocin cells and reduces peripheral release of oxytocin, but induces oxytocin release from dendrites. Dendritic oxytocin release can be triggered by agents that mobilize intracellular calcium. Oxytocin, like -MSH, mobilises intracellular calcium stores in oxytocin cells, and triggers presynaptic inhibition of afferent inputs that is mediated by cannabinoids, and we hypothesized that this mechanism might underlie the inhibitory effects of -MSH. To test this, we recorded extracellularly from identified oxytocin and vasopressin cells in the anesthetised rat SON. Retrodialysis of a CB1 receptor antagonist to the SON blocked the inhibitory effects of i.c.v. injections of -MSH on the spontaneous activity of oxytocin cells. We then monitored synaptically-mediated responses of SON cells to stimulation of the organum vasculosum of the lamina terminalis (OVLT); this evoked a mixed response comprising an inhibitory component mediated by GABA and an excitatory component mediated by glutamate, as identified by the effects of bicuculline and CNQX applied to the SON by retrodialysis. Application of CB1 receptor agonists to the SON attenuated the excitatory effects of OVLT stimulation in both oxytocin and vasopressin cells; while -MSH attenuated the responses of oxytocin cells only. Thus -MSH can act as a 'switch', it triggers oxytocin release centrally but at the same time, through initiating endocannabinoid production in oxytocin cells, inhibits their electrical activity and hence peripheral secretion.