Showing papers by "Ralph J. DiLeone published in 2005"
TL;DR: A novel hypothalamic-AcSh circuit that influences appetitive behavior and mediates the antidepressant activity of MCH1R antagonists is identified and identified, suggesting that these neurons are responsive to a specific set of physiologically relevant conditions.
Abstract: Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a prominent role in feeding and energy homeostasis. The rodent MCH receptor (MCH1R) is highly expressed in the nucleus accumbens shell (AcSh), a region that is important in the regulation of appetitive behavior. Here we establish a role for MCH and MCH1R in mediating a hypothalamic-limbic circuit that regulates feeding and related behaviors. Direct delivery of an MCH1R receptor antagonist to the AcSh blocked feeding and produced an antidepressant-like effect in the forced swim test, whereas intra-AcSh injection of MCH had the opposite effect. Expression studies demonstrated that MCH1R is present in both the enkephalin- and dynorphin-positive medium spiny neurons of the AcSh. Biochemical analysis in AcSh explants showed that MCH signaling blocks dopamine-induced phosphorylation of the AMPA glutamate receptor subunit GluR1 at Ser845. Finally, food deprivation, but not other stressors, stimulated cAMP response element-binding protein-dependent pathways selectively in MCH neurons of the hypothalamus, suggesting that these neurons are responsive to a specific set of physiologically relevant conditions. This work identifies a novel hypothalamic-AcSh circuit that influences appetitive behavior and mediates the antidepressant activity of MCH1R antagonists.
317 citations
01 Jan 2005
TL;DR: Data is presented suggesting a role for ORX/HCRT in opioid dependence and these studies paint a more complete picture of the function of ORX-HCRT and may provide additional targets for therapeutic manipulation of drug dependence.
Abstract: The ORX/HCRT/hypocretin (ORX/HCRT) neuropeptides are regulators of neuronal function and animal behavior. While their function in sleep and regulation of arousal is well studied, the broad projection patterns of the ORX/HCRT neurons suggest that the peptides have the potential to modulate diverse sets of behavior. Moreover, the expression of ORX/HCRT in the lateral hypothalamus (LH) is an indication that the neuropeptide may have an important role in a modulating a broad set of motivated behaviors. Many studies have suggested that the LH is a powerful brain center that has influence over an array of behavioral outputs. In this chapter, data is presented suggesting a role for ORX/HCRT in opioid dependence. These studies paint a more complete picture of the function of ORX/HCRT and may provide additional targets for therapeutic manipulation of drug dependence.