GABA(A) receptor function in the cerebral cortex of alcohol-naive P and NP rats.
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.
Thielen
R J
RJ
Department of Psychiatry, The Institute of Psychiatric Research, Indiana University School of Medicine and the VA Medical Center, Indianapolis 46202-4887, USA.
McBride
W J
WJ
Lumeng
L
L
Li
T K
TK
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D002713:Chlorine; D002755:Choice Behavior / Q000502:physiology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011868:Radioisotopes; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011868:Radioisotopes; D011963:Receptors, GABA-A; D000431:Ethanol; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D010424:Pentobarbital; D010634:Phenobarbital