Affiliation:
1. Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Chile
2. Research Center for the Study of Alcohol Drinking Behavior in Adolescents, Santiago, Chile
Abstract
Background:
High ethanol intake induces a neuroinflammatory response resulting in the subsequent
maintenance of chronic alcohol consumption. The melanocortin system plays a pivotal role in the modulation of
alcohol consumption. Interestingly, it has been shown that the activation of melanocortin-4 receptor (MC4R) in
the brain decreases the neuroinflammatory response in models of brain damage other than alcohol consumption,
such as LPS-induced neuroinflammation, cerebral ischemia, glutamate excitotoxicity, and spinal cord injury.
Objectives:
In this work, we aimed to study whether MC4R activation by a synthetic MC4R-agonist peptide
prevents ethanol-induced neuroinflammation, and if alcohol consumption produces changes in MC4R expression
in the hippocampus and hypothalamus.
Methods:
Ethanol-preferring Sprague Dawley rats were selected offering access to 20% ethanol on alternate days
for 4 weeks (intermittent access protocol). After this time, animals were i.p. administered an MC4R agonist peptide
in the last 2 days of the protocol. Then, the expression of the proinflammatory cytokines interleukin 6 (IL-6),
interleukin 1-beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus, hypothalamus
and prefrontal cortex. It was also evaluated if ethanol intake produces alterations in the expression of
MC4R in the hippocampus and the hypothalamus.
Results:
Alcohol consumption increased the expression of MC4R in the hippocampus and the hypothalamus. The
administration of the MC4R agonist reduced IL-6, IL-1β and TNF-α levels in hippocampus, hypothalamus and
prefrontal cortex, to those observed in control rats that did not drink alcohol.
Conclusion:
High ethanol consumption produces an increase in the expression of MC4R in the hippocampus and
hypothalamus. The administration of a synthetic MC4R-agonist peptide prevents neuroinflammation induced by
alcohol consumption in the hippocampus, hypothalamus, and prefrontal cortex. These results could explain the
effect of α-MSH and other synthetic MC4R agonists in decreasing alcohol intake through the reduction of the
ethanol-induced inflammatory response in the brain.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Cited by
10 articles.
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