GABA(A) receptor function in the cerebral cortex of alcohol-naive P and NP rats

R. J. Thielen, W. J. McBride, L. Lumeng, T. K. Li

Research output: Contribution to journalArticle

6 Scopus citations

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 gM; E(max) = 30.8 ± 1.3 and 28.1 ± 0.9 nmol Cl-/mg protein/3 s, respectively). Pentobarbital (30 μM) 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.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume59
Issue number1
DOIs
StatePublished - Jan 1 1998

Keywords

  • Alcohol-preferring rats
  • Chloride influx
  • GABA(A) receptors
  • Pentobarbital
  • Phenobarbital

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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