Oxytocin Controls Male Sexual Activity via Non-Synaptic Axonal Release in the Spinal Cord

There is considerable current interest concerning the role of the neuropeptide oxytocin in the regulation of socio-sexual behaviors in mammals, ranging from social bonding  to empathy. However, the precise mechanisms by which sparsely dispersed oxytocin fibers in the central nervous system lead to activation of distributed receptor populations are unclear. Here we present evidence, in rats, that release of oxytocin in the lumbar spinal cord is not limited to synapses, but occurs from axonal varicosities and acts by diffusion – a localized volume transmission – to reach oxytocin receptors and facilitate male sexual function. Although somato-dendritic release of oxytocin has been reported in the hypothalamus, our findings demonstrate for the first time that extra-synaptic release occurs from axons in the spinal cord, far distant from the somata and dendrites, to modulate male sexual activity during copulatory behavior.