Melanin-Concentrating Hormone and Its MCH-1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake

• Published in: Alcoholism, clinical and experimental research Vol. 40; no. 10; pp. 2199 - 2207
• Main Authors: Karlsson, Camilla, Aziz, Abdul Maruf Asif, Rehman, Faazal, Pitcairn, Caleb, Barchiesi, Riccardo, Barbier, Estelle, Wendel Hansen, Mikaela, Gehlert, Don, Steensland, Pia, Heilig, Markus, Thorsell, Annika
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2016; Wiley Subscription Services, Inc
• Subjects: Alcohol Drinking - physiopathology; Alcohol Escalation; Alcohol use; Animals; Calorie Intake; Eating - physiology; Energy Intake - physiology; Gene expression; Gene Expression - drug effects; Gene Expression - physiology; Hypothalamic Hormones - biosynthesis; Hypothalamic Hormones - physiology; Hypothalamus - metabolism; Male; Medicin och hälsovetenskap; Melanin-Concentrating Hormone Receptor-1; Melanins - biosynthesis; Melanins - physiology; Motivation; Motivation - physiology; Nucleus Accumbens - metabolism; Pituitary Hormones - biosynthesis; Pituitary Hormones - physiology; Pyrimidinones - pharmacology; Rats; Receptors, Somatostatin - antagonists & inhibitors; Receptors, Somatostatin - physiology; Reward; Rodents; Self Administration; Thiophenes - pharmacology; Melanin-Concentrating Hormone Receptor-1; Calorie Intake; Alcohol Escalation; Reward; Motivation
• ISSN: 0145-6008; 1530-0277; 1530-0277
• DOI: 10.1111/acer.13181

Background Reward and energy homeostasis are both regulated by a network of hypothalamic neuropeptide systems. The melanin‐concentrating hormone (MCH) and its MCH‐1 receptor (MCH1‐R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH1‐R in regulation of caloric intake and motivation to consume alcohol in states of escalated consumption. Methods Rats had intermittent access (IA) to alcohol and were divided into high‐ and low‐drinking groups. Food and alcohol consumption was assessed after administration of an MCH1‐R antagonist, GW803430. Next, GW803430 was evaluated on alcohol self‐administration in protracted abstinence induced by IA in high‐drinking rats. Finally, the effect of GW803430 was assessed on alcohol self‐administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH1‐R was measured in the hypothalamus and nucleus accumbens (NAc) in both acute and protracted abstinence. Results High‐drinking IA rats consumed more calories from alcohol than chow and GW803430 decreased both chow and alcohol intake. In low‐drinking rats, only food intake was affected. In protracted abstinence from IA, alcohol self‐administration was significantly reduced by pretreatment with GW803430 and gene expression of both MCH and the MCH1‐R were dysregulated in hypothalamus and NAc. In contrast, during acute withdrawal from vapor exposure, treatment with GW803430 did not affect alcohol self‐administration, and no changes in MCH or MCH1‐R gene expression were observed. Conclusions Our data suggest a dual role of MCH and the MCH1‐R in regulation of alcohol intake, possibly through mechanisms involving caloric intake and reward motivation. A selective suppression of alcohol self‐administration during protracted abstinence by GW803430 was observed and accompanied by adaptations in gene expression of MCH and MCH1‐R. Selective suppression of escalated consumption renders the MCH1‐R an attractive target for treatment of alcohol use disorders.