Decreased 5-HT2cR and GHSR1a interaction in antipsychotic drug-induced obesity.

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Obesity reviews : an official journal of the International Association for the Study of Obesity, ISSN: 1467-789X, Vol: 19, Issue: 3, Page: 396-405

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Huang, Xu-Feng; Weston-Green, Katrina; Yu, Y
Medicine; decreased; 5‐ht2cr; interaction; ghsr1a; antipsychotic; obesity; drug‐induced; Medicine and Health Sciences
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Second generation antipsychotics (SGAs), notably atypical antipsychotics including olanzapine, clozapine and risperidone, can cause weight gain and obesity side effects. Antagonism of serotonin 2c receptors (5-HT2cR) and activation of ghrelin receptor type 1a (GHSR1a) signalling have been identified as a main cause of SGA induced obesity. Here we review the pivotal regulatory role of the 5-HT2cR in ghrelin-mediated appetite signalling. The 5-HT2cR dimerizes with GHSR1a to inhibit orexigenic signalling, while 5-HT2cR antagonism reduces dimerization and increases GHSR1a-induced food intake. Dimerization is specific to the unedited 5-HT2cR isoform. 5-HT2cR antagonism by SGAs may disrupt the normal inhibitory tone on the GHSR1a, increasing orexigenic signalling. The 5-HT2cR and its interaction with the GHSR1a could serve as the basis for discovering novel approaches to preventing and treating SGA-induced obesity.