Activation of TRPV1 in the VTA excites dopaminergic neurons and increases chemical-and noxious-induced dopamine release in the nucleus accumbens

Dopamine (DA)-containing neurons of the ventral tegmental area (VTA) provide dopaminergic input to the nucleus accumbens and to the prefrontal cortex within the mesolimbic pathway, In the present study, we combined eiectrophysiological recordings and microdialysis techniques to investigate the function of transient receptor potential vanilloid I (TRPV1) channel in the VTA. In brain slices, application of the TRPV1 receptor agonist capsaicin increased the firing rate of rat dopamine neurons and in a proportion of tested cells (44%) it also induced a bursting behavior. The effects of capsaicin were concentration dependent. The increase in neuronal firing was dependent on enhanced glutamatergic transmission since it was blocked by the super-fusion of the ionotropic glutamate antagonists, CNQX and AP5. Interestingly, microinjection of capsaicin into the VTA and noxious tail stimulation transiently enhanced dopamine release into the nucleus accumbens. Both the in vitro and in vivo effects were mediated by TRPV1 activation in the VTA since they were reduced by co-perfusion of the selective TRPV1 receptor antagonist odoresineferatoxin. Our data suggest a novel role for TRPV1 channels in the mesencephalon of rat, namely activation of the DA system following a peripheral noxious stimulation.