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Decreased Immunoreactivity of the Melanocortin Neuropeptide α‐Melanocyte‐Stimulating Hormone (α‐MSH) After Chronic Ethanol Exposure in Sprague–Dawley Rats
Author(s) -
Navarro Montserrat,
Cubero Inmaculada,
Knapp Darin J.,
Breese George R.,
Thiele Todd E.
Publication year - 2008
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/j.1530-0277.2007.00578.x
Subject(s) - medicine , endocrinology , melanocortin , neuropeptide , proopiomelanocortin , hypothalamus , ethanol , chemistry , melanocyte stimulating hormone , receptor , central nucleus of the amygdala , hormone , biology , biochemistry
Background: The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor proopiomelanocortin (POMC). Recent pharmacologic and genetic evidence suggests that MC receptor (MCR) signaling modulates neurobiologic responses to ethanol and ethanol intake. Because ethanol decreases POMC mRNA levels, we determined if exposure to an ethanol‐containing diet (ED) would significantly reduce central immunoreactivity of the MC peptide α‐MSH in rats. We also determined if ethanol exposure would alter the immunoreactivity of agouti‐related protein (AgRP), an endogenous MCR antagonist. Methods: Male Sprague–Dawley rats were given 18 days of access to normal rodent chow or a control diet (CD), or short‐term (4 days) or long‐term (18 days) access to an ED. At the end of the study, rats were perfused with 4% paraformaldehyde and their brains were sectioned into two sets for processing with α‐MSH or AgRP immunohistochemistry. Results: Rats exposed to an ED showed significant reductions of central α‐MSH immunoreactivity relative to rats exposed to a control diet (CD) or normal rodent chow. Ethanol‐induced reductions of α‐MSH immunoreactivity were site‐specific and were noted in regions of the hypothalamus and extended amygdala, as well as the paraventricular nucleus of the thalamus. Because there were no differences in body weights or caloric intake between the CD and ED groups, reductions of α‐MSH immunoreactivity in ED‐treated rats are best explained by ethanol exposure rather than altered energy balance. No significant ethanol‐induced alterations in hypothalamic AgRP immunoreactivity were detected. Conclusions: The present study shows that ethanol site specifically reduces α‐MSH immunoreactivity in rat brain. These observations, in tandem with recent pharmacologic and genetic studies, suggest that the endogenous MC system modulates neurobiologic responses to ethanol. Thus, compounds which target MCRs may prove to have therapeutic value in the treatment of excessive ethanol consumption and/or the symptoms associated with ethanol withdrawal.