Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat: Historical perspective.

UNLABELLED: Since the publication of the observation that dopaminergic neurons in the ventral tegmental area/substantia nigra of the rat express receptors for insulin and leptin, numerous studies have extended and validated these findings. Thus, these major metabolic hormones have effects on synaptic and cell signaling function of the midbrain dopamine neurons, across a range of concentrations that reflect physiologic (fasting vs. fed) and pathophysiologic (diabetes) circumstances. The capacity of metabolic hormones to alter reward behaviors, including palatability-related food intake; motivation for food; and the conditioning of place preference by food, is now appreciated as an integral part of the larger actions of these hormones to regulate caloric homeostasis. Finally, the delineation of metabolic hormone effects on the CNS reward circuitry of normal animals provides the rationale and experimental basis for evaluating dysfunction of reward circuitry in obesity and diabetes. ORIGINAL ARTICLE ABSTRACT: EXPRESSION OF RECEPTORS FOR INSULIN AND LEPTIN IN THE VENTRAL TEGMENTAL AREA/SUBSTANTIA NIGRA (VTA/SN) OF THE RAT: Recent studies have demonstrated that the metabolic hormones insulin and leptin can modulate behavioral performance in reward-related paradigms. However, specific anatomical substrate(s) within the CNS for these effects remain to be identified. We hypothesize that midbrain dopamine neurons, which have been implicated to be critical in the mediation of motivational and reward aspects of stimuli, contribute to these behavioral effects of insulin and leptin. As one approach to evaluate this hypothesis, we used double-labeling fluorescence immunohistochemistry to determine whether the midbrain dopamine neurons express insulin receptors or leptin receptors. Extensive co-expression of tyrosine hydroxylase (a marker for dopamine neurons) with both the insulin receptor and the leptin receptor was observed in the ventral tegmentum and substantia nigra. These findings suggest that midbrain dopamine neurons are direct targets of insulin and leptin, and that they participate in mediating the effects of these hormones on reward-seeking behavior. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Published by Elsevier B.V.