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
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.