Voluntary alcohol drinking enhances proopiomelanocortin gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats.
BACKGROUND
Evidence obtained in humans and rodents indicates that beta-endorphin (encoded by the proopiomelanocortin [POMC] gene) is critical in the regulation of alcohol drinking behavior. However, the alcohol effect on POMC gene expression has not been studied in rodent mesolimbic regions, such as the nucleus accumbens (NAc).


METHODS
In this study, we first utilized POMC-enhanced green fluorescent protein (EGFP) transgenic mice to visualize POMC neurons and found that POMC-EGFP cells were modestly distributed throughout the NAc shell and core, in addition to the hypothalamic arcuate nucleus. POMC mRNA expression in the NAc of mice and rats was confirmed using reverse transcriptase-polymerase chain reaction and solution hybridization assays. We then investigated whether there are genetically determined differences in basal mRNA levels of POMC and mu opioid receptor (MOP-r) between selectively bred Sardinian alcohol-preferring (sP) and nonpreferring (sNP) rats, and whether these mRNA levels are altered in sP rats after alcohol drinking (10%, unlimited access) for 17 days.


RESULTS
Alcohol-naïve sP rats had higher basal POMC mRNA levels than sNP rats only in hypothalamus. Alcohol drinking increased POMC mRNA levels in both the NAc shell (by 100%) and the hypothalamus (by 50%) of sP rats. Although sP rats had lower basal levels of MOP-r mRNA and GTPγS binding in NAc shell than sNP rats, voluntary alcohol consumption had no effect on MOP-r mRNA levels in the NAc shell.


CONCLUSIONS
Our results define the distribution of POMC-expressing neurons in the NAc of mice and rats. Higher POMC expression at basal levels in sP rats (genetically determined), along with increases after drinking (alcohol-induced) in the NAc shell and hypothalamus, suggests that the POMC systems play a role in high alcohol preference and consumption.
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10065, USA. yan.zhou@rockefeller.edu
Yan
Y
Zhou
Giancarlo
G
Colombo
Keiichi
K
Niikura
Mauro A M
MA
Carai
Teresa
T
Femenía
Maria S
MS
García-Gutiérrez
Jorge
J
Manzanares
Ann
A
Ho
Gian Luigi
GL
Gessa
Mary Jeanne
MJ
Kreek
D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D000431:Ethanol; D011333:Pro-Opiomelanocortin