Decreased immunoreactivity of the melanocortin neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) after chronic ethanol exposure in Sprague-Dawley rats.
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 alpha-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 alpha-MSH or AgRP immunohistochemistry.


RESULTS
Rats exposed to an ED showed significant reductions of central alpha-MSH immunoreactivity relative to rats exposed to a control diet (CD) or normal rodent chow. Ethanol-induced reductions of alpha-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 alpha-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 alpha-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.
Navarro
Montserrat
M
Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599-3270, USA.
Cubero
Inmaculada
I
Knapp
Darin J
DJ
Breese
George R
GR
Thiele
Todd E
TE
D054369:Agouti-Related Protein / Q000032:analysis; D000437:Alcoholism / Q000473:pathology*; D000679:Amygdala / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002452:Cell Count; D007031:Hypothalamus / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D009042:Motivation; D009474:Neurons / Q000473:pathology; D010487:Periaqueductal Gray / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012686:Septal Nuclei / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D013788:Thalamus / Q000473:pathology; D000521:alpha-MSH / Q000032:analysis*
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D000521:alpha-MSH