DEVELOPMENT OF GABA(A) RECEPTORS ON MEDIAL SEPTUM DIAGONAL BAND (MS/DB) NEURONS AFTER POSTNATAL ETHANOL EXPOSURE/

The impact of 'binge-like' ethanol exposure on postnatal days (PD) 4-9 was examined on development of gamma-aminobutyric acid type A recepto rs (GABA(A)R) during the first month of life in the rat. Whole-cell pa tch-clamp recordings in acutely isolated medial septum/diagonal band ( MS/DB) neurons were used to define effects of rapidly applied ethanol and other allosteric modulators on bicuculline-sensitive GABA currents . Three age groups were examined including 'pups' (PD 4-10), 'juvenile s' (PD 11-16) and 'young adults' (PD 25-35). In untreated neurons, max imum responses to GABA and the apparent GABA EC50 increased similar to 2-fold during the first month of life. Potentiation of GABA responses by pentobarbital, midazolam, and loreclezole all increased with age, while Zn2+ inhibition declined. Initial inhibition by ethanol switched to potentiation of GABA responses during this time. In vivo, binge-li ke ethanol treatment (4.5 g kg(-1) day(-1) divided into two doses, 2 h apart on PD 4-9) reduced both the GABA maximal response and GABA EC50 measured on PD 11-16. These measures returned to control levels by PD 25-35. After binge-like postnatal ethanol exposure, age-dependent los s of Zn2+ inhibition of GABA responses was increased, while potentiati ng actions of in vitro ethanol were blocked. GABA(A)R modulation by ot her drugs was unaffected. These data suggest that early postnatal etha nol exposure disrupts the expected developmental pattern of GABA(A)R f unction in MS/DB neurons, an action that could contribute to neurobeha vioral deficits associated with the fetal alcohol syndrome. Whether th ese changes are due to cellular damage, delayed gene expression or pos t-translational modification needs to be determined. (C) 1998 Elsevier Science B.V. All rights reserved.