Insulin in the ventral tegmental area reduces cocaine-evoked dopamine in the nucleus accumbens in vivo.

Mesolimbic dopamine circuits, implicated in incentive motivation, are sensitive to changes in metabolic state such as weight loss and diet-induced obesity. These neurons are important targets for metabolic hormones such as leptin, glucagon-like peptide-1, ghrelin and insulin. Insulin receptors are located on dopamine neurons in the ventral tegmental area (VTA) and we have previously demonstrated that insulin induces long-term depression of excitatory synapses onto VTA dopamine neurons. While insulin can decrease dopamine concentration in somatodendritic regions, it can increase dopamine in striatal slices. Whether insulin directly targets the VTA to alter dopamine release in projection areas, such as the nucleus accumbens (NAc), remains unknown. The main goal of the present experiments was to examine NAc dopamine concentration following VTA administration of insulin. Using in vivo FSCV to detect rapid fluctuations in dopamine concentration, we showed that intra-VTA insulin via action at insulin receptors reduced pedunculopontine nucleus-evoked dopamine release in the NAc. Furthermore, intra-VTA insulin reduced cocaine-potentiated NAc dopamine. Finally, intra-VTA or intranasal insulin decreased locomotor responses to cocaine, an effect blocked by an intra-VTA administered insulin receptor antagonist. Together, these data demonstrate that mesolimbic dopaminergic projections are important targets of the metabolic hormone, insulin.