Signaling in rat brainstem via Gpr160 is required for the anorexigenic and antidipsogenic actions of cocaine- and amphetamine-regulated transcript peptide

Abstract

Recent work identified Gpr160 as a candidate receptor for cocaine- and amphetamine-regulated transcript peptide (CARTp) and described its role in pain modulation. The aims of the present study were to determine if Gpr160 is required for the CARTp’s ability to reduce food intake and water intake and to initially identify the distribution of Gpr160-like immunoreactivity (Gpr160ir) in the rat brain. A passive immunoneutralization approach targeting Gpr160 was used to block the behavioral effects of a pharmacological dose of CARTp in the fourth cerebroventricle (4V) of rats and to determine the importance of endogenously produced CARTp in the control of ingestive behaviors. Passive immunoneutralization of Gpr160 in the 4V blocked the actions of CARTp to inhibit food intake and water intake. Blockade of Gpr160 in the 4V, independent of pharmacological CART treatment, caused an increase in both overnight food intake and water intake. The decrease in food intake, but not water intake, caused by central injection of CARTp was demonstrated to be interrupted by prior administration of a glucagon-like peptide 1 (GLP-1) receptor antagonist. Gpr160ir was observed in several, distinct sites throughout the rat brain, where CARTp staining has been described. Importantly, Gpr160ir was observed to be present in both neuronal and nonneuronal cell types. These data support the hypothesis that Gpr160 is required for the anorexigenic actions of central CARTp injection and extend these findings to water drinking. Gpr160ir was observed in both neuronal and nonneuronal cell types in regions known to be important in the multiple pharmacological effects of CARTp, identifying those areas as targets for future compromise of function studies.