Persistent reduction of GABA(A) receptor-mediated inhibition in rat hippocampus after chronic intermittent ethanol treatment.

Published

Journal Article

GABA(A) receptor-mediated function was studied in rats treated with chronic intermittent ethanol (CIE). Rats were given 60 doses of 6g/kg ethanol every 24 h by gastric intubation, with repeated intoxicating and withdrawal episodes leading to a kindling-like increase in seizure susceptibility (Kokka et al., Alcohol: Clin. Exp. Res., 17 (1993) 525-531). Efflux of 36Cl-, evoked by application of muscimol, a measure of GABA(A) receptor function, was examined in 300 mu m slices obtained from frontal, parietal, and temporal cortex, hippocampus, and inferior colliculus, one day after the last administration of ethanol. Compared to controls, the 36Cl- efflux in hippocampal slices of CIE rats was significantly reduced by 29%, while there were no changes in the other brain regions studied. In hippocampal slices, paired-pulse inhibition in CA1 pyramidal neurons, measured extracellularly using homosynaptic orthodromic stimulation at an interval of 10 ms, was significantly reduced in CIE rats. A significant decrease by 40% both at 2 and 40 days after 60 doses of ethanol was found, implying a persistent decrease in GABA(A) receptor-mediated inhibition in CIE rats. These reductions in paired-pulse inhibition are consistent with the decrease in the pentylenetetrazol (PTZ) seizure threshold which was previously observed in CIE rats. Therefore, we suggest that this reduction of GABA(A) receptor-mediated inhibition contributes to the persistent increase in seizure susceptibility of CIE rats.

Full Text

Cited Authors

  • Kang, M; Spigelman, I; Sapp, DW; Olsen, RW

Published Date

  • February 1996

Published In

Volume / Issue

  • 709 / 2

Start / End Page

  • 221 - 228

PubMed ID

  • 8833758

Pubmed Central ID

  • 8833758

Electronic International Standard Serial Number (EISSN)

  • 1872-6240

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/0006-8993(95)01274-5

Language

  • eng