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Voluntary alcohol drinking enhances proopiomelanocortin gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats.

ABSTRACT: 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).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.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 GTP?S binding in NAc shell than sNP rats, voluntary alcohol consumption had no effect on MOP-r mRNA levels in the NAc shell.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.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC3777244 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Voluntary alcohol drinking enhances proopiomelanocortin gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats.

Zhou Yan Y Colombo Giancarlo G Niikura Keiichi K Carai Mauro A M MA Femenía Teresa T García-Gutiérrez Maria S MS Manzanares Jorge J Manzanares Jorge J Ho Ann A Gessa Gian Luigi GL Kreek Mary Jeanne MJ

Alcoholism, clinical and experimental research 20120622

<h4>Background</h4>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).<h4>Methods</h4>In this study, we first utilized POMC-enhanced green fluorescent protein (EGFP) transgenic mice to visualize POMC neurons and found that POMC-EGFP ...[more]

PMID: 22724395

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Project description:The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions for 5 consecutive days each week until they were 49 days old. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 ‚Äì 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in the in biological processes involved in cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis (WGCNA) indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce long-term changes in neuronal function. Differences in gene expression in brain nucleus accumbens shell (Acb-sh) were compared in two groups of alcohol-preferring (P) rats, one given water only and the other given access to 15 & 30% ethanol during adolescence.

Dataset Information

Voluntary alcohol drinking enhances proopiomelanocortin gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats.

Publications

Voluntary alcohol drinking enhances proopiomelanocortin gene expression in nucleus accumbens shell and hypothalamus of Sardinian alcohol-preferring rats.

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