Postnatal ethanol exposure blunts upregulation of GABA(A) receptor currents in Purkinje neurons

Recently, we found that early postnatal ethanol exposure inhibits the matur ation of GABA(A) receptors (GABA(A)Rs) in developing medial septum/diagonal band (MS/DB) neurons, suggesting that these receptors may represent a targ et for ethanol related to fetal alcohol syndrome (FAS). To determine whethe r GABA(A)Rs on other neurons are also sensitive to a postnatal ethanol insu lt, postnatal day (PD) 4-9, rat pups were artificially reared and exposed t o ethanol (4.5 g kg(-1) day(-1), 10.2% v/v). The pharmacological profile of acutely dissociated cerebellar Purkinje cell GABA(A)Rs from untreated, art ificially reared controls and ethanol-treated animals was examined with con ventional whole-cell patch clamp recordings during PD 12-16 (juveniles) and PD 25-35 (young adults). For untreated animals, GABA (0.3-100 mu M) consis tently induced inward Cl- currents in a concentration-dependent manner show ing an age-related increase in maximum response without change in EC50 or s lope value. Acute ethanol (100 mM) consistently inhibited 3 mu M GABA curre nts (10-20%); positive modulators, pentobarbital (10 mu M), midazolam (1 mu M) and loreclezole (10 mu M), consistently potentiated; the negative modul ator, Zn2+ (30 mu M), inhibited GABA currents across both juvenile and youn g adult groups. Loreclezole potentiation increased while Zn2+ inhibition de creased with age in untreated Purkinje neurons. Postnatal ethanol exposure (PD 4-9) decreased GABA(A)R maximum current density in young adult Purkinje cells but not in juvenile neurons. However, sensitivity to allosteric modu lators did not change after ethanol. These data are consistent with the hyp othesis that postnatal ethanol exposure during the brain growth spurt can d isturb GABA(A)R development across the brain, although the mechanism(s) und erlying this action remains to be determined. (C) 1999 Elsevier Science B.V . All rights reserved.