Distribution and Activation of Melanin-Concentrating Hormone Receptor-1 at Dopaminergic, GABAergic, and Glutamatergic Neurons in the Ventral Tegmental Area

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide that acts through its receptor (MCHR1) to promote positive energy balance. MCH can inhibit dopamine release from the mesocorticolimbic dopamine pathway originating in the ventral tegmental area (VTA), and a hyperdopaminergic state underlies hyperactivity in animals lacking MCH or MCHR1. It is not known if the inhibitory effect of MCH on dopaminergic tone could be due to direct regulation of dopaminergic VTA neurons. We used a combination of molecular, neuroanatomical, and electrophysiological techniques to assess MCHR1 expression and activation in the VTA. We detected MCH projections to the VTA and, MCHR1 expression on dopaminergic, GABAergic, and glutamatergic VTA neurons, demonstrating potential sites of MCH-release and action, respectively. Furthermore, MCHR1 activation may regulate dopamine release by directly inhibiting dopaminergic VTA neurons, and by disinhibiting glutamatergic afferents to dopaminergic VTA neurons. These results signify that the VTA is a novel target for MCH-mediated physiology.