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Melanin‐Concentrating Hormone and Its MCH ‐1 Receptor: Relationship Between Effects on Alcohol and Caloric Intake
Author(s) -
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
Publication year - 2016
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13181
Subject(s) - endocrinology , alcohol , calorie , medicine , abstinence , hypothalamus , hormone , nucleus accumbens , melanin concentrating hormone , ethanol , energy homeostasis , self administration , antagonist , receptor , neuropeptide , chemistry , biochemistry , psychiatry
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 ( MCH 1‐R) modulate alcohol intake, but it remains unknown to what extent this reflects actions on energy balance or reward. Here, we evaluated the MCH 1‐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 MCH 1‐R antagonist, GW 803430. Next, GW 803430 was evaluated on alcohol self‐administration in protracted abstinence induced by IA in high‐drinking rats. Finally, the effect of GW 803430 was assessed on alcohol self‐administration in acute withdrawal in rats exposed to alcohol vapor. Gene expression of MCH and MCH 1‐R was measured in the hypothalamus and nucleus accumbens ( NA c) in both acute and protracted abstinence. Results High‐drinking IA rats consumed more calories from alcohol than chow and GW 803430 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 GW 803430 and gene expression of both MCH and the MCH 1‐R were dysregulated in hypothalamus and NA c. In contrast, during acute withdrawal from vapor exposure, treatment with GW 803430 did not affect alcohol self‐administration, and no changes in MCH or MCH 1‐R gene expression were observed. Conclusions Our data suggest a dual role of MCH and the MCH 1‐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 GW 803430 was observed and accompanied by adaptations in gene expression of MCH and MCH 1‐R. Selective suppression of escalated consumption renders the MCH 1‐R an attractive target for treatment of alcohol use disorders.