Chronic ethanol consumption alters recovery of spontaneously active medialseptal/diagonal band of broca neurons from GABA-microiontophoresis

Citation
Db. Matttews et al., Chronic ethanol consumption alters recovery of spontaneously active medialseptal/diagonal band of broca neurons from GABA-microiontophoresis, ALC CLIN EX, 24(9), 2000, pp. 1427-1432
Citations number
58
Categorie Soggetti
Clinical Psycology & Psychiatry","Neurosciences & Behavoir
Journal title
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
ISSN journal
01456008 → ACNP
Volume
24
Issue
9
Year of publication
2000
Pages
1427 - 1432
Database
ISI
SICI code
0145-6008(200009)24:9<1427:CECARO>2.0.ZU;2-3
Abstract
Background: Acute ethanol administration increases GABA-mediated inhibition in a variety of cerebral cortical preparations. Furthermore, chronic ethan ol administration blunts ethanol-induced increases in GABA-mediated inhibit ion and alters GABA(A) receptor subunit mRNA and peptide expression in the cerebral cortex. The sedative hypnotic effects of ethanol are believed to b e modulated by GABA-induced inhibition in medial septum/diagonal band of Br oca (MS/DB) neurons, a brain region where acute ethanol administration incr eases GABA-mediated inhibition of spontaneously active neurons. Chronic eth anol administration produces tolerance to the sedative effects of ethanol. However, it is unknown if chronic ethanol consumption produces alterations in GABA-mediated inhibition in the MS/DB in a manner similar to that found in the cerebral cortex. Methods: Animals either consumed ethanol chronically for 14 days via a liqu id diet or were pair-fed an equicaloric dextrose-containing control, diet. Spontaneously active MS/DB neurons were recorded using multibarrel glass mi cropipettes while the effect of GABA-microiontophoresis was investigated. T he total amount of GABA-mediated inhibition at four ejection currents was a nalyzed, as was the recovery to spontaneous neural firing rates following G ABA inhibition. In a separate group of animals, the medial septum was micro dissected, and the relative expression of GABA(A) receptor alpha 1 and alph a 4 subunit peptide were analyzed via Western blot analysis. Results: Chronic ethanol consumption altered recovery of spontaneous neural activity of MS/DB neurons following GABA-microiontophoresis compared to pr emicroiontophoresis levels. Specifically, the recovery of spontaneous neura l activity of MS/DB neurons recorded from animals that chronically consumed ethanol was slower following GABA-microiontophoresis compared to neurons r ecorded from control animals. This effect was temporary and reversible. Fur thermore, the alteration in recovery of spontaneous neural activity was not due to changes in the total amount of inhibition produced by GABA. Finally , there was no significant change in GABA(A) receptor alpha 1 and alpha 4 s ubunit peptide levels in the MS/DB. Conclusions: Chronic ethanol consumption alters the frequency of spontaneou s MS/DB neural activity following GABA microiontophoresis compared to premi croiontophoresis levels. These data suggest that the kinetics of GABA(A) re ceptors in the MS/DB are altered by chronic ethanol consumption independent of changes in the total amount of inhibition or alterations in GABA(A) rec eptor alpha 1 and alpha 4 subunit peptide expression.