Melanin-concentrating hormone (MCH) is a cyclic peptide produced in the lateral hypothalamus. It has been implicated in a number of physiological processes including feeding behavior, energy balance, and the regulation of emotional states. (1-10 mg/kg) significantly reduced immobility time in the forced swimming test in rats, indicating antidepressantlike effects. Both ATC0065 and ATC0175 significantly reversed swim stress-induced anxiety in the elevated plus-maze test in rats and stress-induced hyperthermia in mice. ATC0175 significantly increased social interaction between unfamiliar rats and reduced separation-induced vocalizations in guinea pig pups, indicating anxiolytic potential. In contrast, ATC0065 and ATC0175 did not affect spontaneous locomotor activity or rotarod performance in rats. These findings indicate that ATC0065 and ATC0175 are potent and orally active MCHR1 antagonists with anxiolytic and antidepressant activity in rodents.Melanin-concentrating hormone (MCH) is a cyclic neuropeptide originally isolated from salmon pituitary (Kawaguchi et al., 1983). In mammals, MCH is produced predominantly by neurons in the lateral hypothalamus and zona incerta with extensive projections throughout the brain (Bittencourt et al., 1992). This expression pattern supports a role for MCH in numerous physiological processes including motivated behavior, stress responses, regulation of neuroendocrine function, and feeding.Several groups independently identified a G protein-coupled receptor, SLC-1/GPR24, as an MCH receptor (MCHR1) (Bachner et al., 1999;Chambers et al., 1999;Lembo et al., 1999;Saito et al., 1999;Shimomura et al., 1999), and MCHR2 was identified subsequently on the basis of the sequence homology to MCHR1 Hill et al., 2001;Mori et al., 2001;Sailer et al., 2001). Potential physiological functions of MCHR2 have not been elucidated due to the species-specific expression of the receptor (Tan et al., 2002); therefore, current research has focused on MCHR1.There are several lines of evidence implicating MCHR1 in feeding and energy homeostasis. MCHR1 mRNA is increased Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
