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Alcohol Clin Exp Res. 2016 Oct;40(10):2199-2207. doi: 10.1111/acer.13181. Epub 2016 Aug 31.

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

Author information

1
Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden. camilla.s.karlsson@liu.se.
2
Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.
3
Laboratory of Clinical and Translational Studies, NIAAA, NIH, Bethesda, Maryland.
4
CNS Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.
5
Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Abstract

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.

KEYWORDS:

Alcohol Escalation; Calorie Intake; Melanin-Concentrating Hormone Receptor-1; Motivation; Reward

PMID:
27579857
DOI:
10.1111/acer.13181
[Indexed for MEDLINE]

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