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  • Title: GABA(A) receptor function in the cerebral cortex of alcohol-naive P and NP rats.
    Author: Thielen RJ, McBride WJ, Lumeng L, Li TK.
    Journal: Pharmacol Biochem Behav; 1998 Jan; 59(1):209-14. PubMed ID: 9443557.
    Abstract:
    Previous studies have demonstrated an innate difference in the sensitivity of ethanol-naive P and NP rats to the acute intoxicating effects of high doses of ethanol. A number of studies have suggested that the acute intoxicating effects of ethanol may be mediated in part through potentiation of GABA(A)/benzodiazepine receptor function. In the present study, the function of GABA(A)/benzodiazepine receptors was studied in ethanol-naive alcohol-preferring (P) and -nonpreferring (NP) lines of rats by measuring 36Cl- influx into cortical microsacs. GABA, in a concentration-dependent manner, increased 36Cl- influx to an equivalent extent into cortical microsacs from P and NP rats (EC50 = 9.0 +/- 1.0 and 10 +/- 1.1 microM; Emax = 30.8 +/- 1.3 and 28.1 +/- 0.9 nmol Cl-/mg protein/3 s, respectively). Pentobarbital (30 microM) enhanced GABA-stimulated 36Cl- uptake (75 and 71% increase for P and NP rats, respectively) equally well in cortical microsacs from P and NP rats. Likewise, phenobarbital potentiation of GABA-stimulated 36Cl- influx was similar in cortical microsacs from P and NP rats. Phenobarbital, at the highest concentration tested (3 mM), directly stimulated 36Cl- influx to a similar extent in P and NP rats. However, ethanol failed to alter GABA-stimulated 36Cl- uptake into cortical microsacs prepared from ethanol-naive P and NP rats. The present results suggest that the differences between P and NP rats in innate sensitivity to the high dose effects of ethanol do not appear to be due to differences in cortical GABA(A) receptor function.
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