Small molecule melanin-concentrating hormone receptor 1 (MCH1R) antagonists as anxiolytic and antidepressive agents

The search for new anxiolytics and antidepressants with a more rapid onset of action has led researchers to pursue neuropeptide receptors as molecular targets for these indications. Among these peptide targets, melanin-concentrating hormone (MCH) has shown promising, albeit inconsistent, data supporting a role for this peptide in human emotional disorders. Neurochemical and neuroanatomical studies have revealed that MCH plays a key role in animal feeding and other behavior; however, alteration of MCH signaling by transgenesis or treatment with endogenous and synthetic MCH1R ligands has produced confounding results in animal models of human emotional disorders. This review describes recent contributions to the understanding of the role of MCH in animal stress response.