AA and ANA rats are one of the earliest and well established rodent models for ethanol preference. Several candidate genes have been suggested to confer genetic susceptibility for alcoholism in these lines including mitogen-activated protein kinases, Akt/PKB and GSK-3 pathways. The aim of the study was to compare the protein levels and phopshorylation of ERK 1/2, Akt and GSK-3 in AA and ANA rats under basal condition and after acute ethanol challenge. Animals were injected with either ethanol (1.5 g/kg) or saline and killed 20 or 45 minutes after injection. Brains were frozen and dissected, nucleus accumbens (NAcc) and cingulate cortex (CCx) were extracted and subject to immunobloting with total and phosphospecifi c antibodies. Baseline differences in ERK 1/2 phopshorylation were discovered between AA and ANA lines. Intraperitoneal injection of ethanol (1.5 g/kg) induced a rapid and transient decrease in ERK 1/2 phosphorylation in both CCx and NAcc within 20 minutes which was already reverting towards control levels at the 45 minute time point. There was no change in the total ERK levels. Phosphorylation of both GSK-3 and Akt in CCx of AA rats was increased 45 minutes after ethanol injection, however no changes were found in NAcc. In ANA rats there were no statistically signifi cant changes in all structures. Thus, AA rats are more susceptible to acute effects of ethanol involving some of the mitogen-activated protein kinases, Akt/PKB and GSK-3 pathways, and these differences are more prominent in the CCx compared to the NAcc.

SIGNAL TRANSDUCTION IN ALCOHOL-PREFERRING AA AND ALCOHOL-AVOIDING ANA RAT LINES

RIMONDINI GIORGINI, ROBERTO;
2007

Abstract

AA and ANA rats are one of the earliest and well established rodent models for ethanol preference. Several candidate genes have been suggested to confer genetic susceptibility for alcoholism in these lines including mitogen-activated protein kinases, Akt/PKB and GSK-3 pathways. The aim of the study was to compare the protein levels and phopshorylation of ERK 1/2, Akt and GSK-3 in AA and ANA rats under basal condition and after acute ethanol challenge. Animals were injected with either ethanol (1.5 g/kg) or saline and killed 20 or 45 minutes after injection. Brains were frozen and dissected, nucleus accumbens (NAcc) and cingulate cortex (CCx) were extracted and subject to immunobloting with total and phosphospecifi c antibodies. Baseline differences in ERK 1/2 phopshorylation were discovered between AA and ANA lines. Intraperitoneal injection of ethanol (1.5 g/kg) induced a rapid and transient decrease in ERK 1/2 phosphorylation in both CCx and NAcc within 20 minutes which was already reverting towards control levels at the 45 minute time point. There was no change in the total ERK levels. Phosphorylation of both GSK-3 and Akt in CCx of AA rats was increased 45 minutes after ethanol injection, however no changes were found in NAcc. In ANA rats there were no statistically signifi cant changes in all structures. Thus, AA rats are more susceptible to acute effects of ethanol involving some of the mitogen-activated protein kinases, Akt/PKB and GSK-3 pathways, and these differences are more prominent in the CCx compared to the NAcc.
2007
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
193A
193A
O. Neznanova; W. Sommer; R. Rimondini; P. Hyytia; M. Heilig
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/112496
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