Neurokinin3 receptor modulation of the behavioral and neurochemical effects of cocaine in rats and monkeys

Neurokinin(3) (NK3) receptors and their endogenous ligands (e.g. the neuropeptide substance P and its C-terminal fragment) have been implicated in psychomotor activity and reinforcement mechanisms. We review here recent findings on the involvement of NK3 receptors in the behavioral and neurochemical effects of cocaine. Although NK3 receptors can modulate dopamine (DA) activity in the brain, recent results suggest that this modulation does not occur during spontaneous behavioral activity. However, NK3 receptors play a role in the regulation of cocaine-induced DA responses in the nucleus accumbens core and shell subregions. NK3 receptor agonism as well as antagonism potentiate cocaine's effects on nucleus accumbens DA subregions specifically, and modulate the acute behavioral effects of cocaine in rats and non-human primates (Callithrix penicillata). However, conditioned place preference studies in rats have, so far, failed to provide evidence for an involvement of NK3 receptors in the reinforcing effects of cocaine.