Abstract
The impact of `binge-like' ethanol exposure on postnatal days (PD) 4–9 was examined on development of γ-aminobutyric acid type A receptors (GABA AR) during the first month of life in the rat. Whole-cell patch-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), `juveniles' (PD 11–16) and `young adults' (PD 25–35). In untreated neurons, maximum responses to GABA and the apparent GABA EC 50 increased ∼2-fold during the first month of life. Potentiation of GABA responses by pentobarbital, midazolam, and loreclezole all increased with age, while Zn 2+ inhibition declined. Initial inhibition by ethanol switched to potentiation of GABA responses during this time. In vivo, binge-like 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 EC 50 measured on PD 11–16. These measures returned to control levels by PD 25–35. After binge-like postnatal ethanol exposure, age-dependent loss of Zn 2+ inhibition of GABA responses was increased, while potentiating actions of in vitro ethanol were blocked. GABA AR modulation by other drugs was unaffected. These data suggest that early postnatal ethanol exposure disrupts the expected developmental pattern of GABA AR function in MS/DB neurons, an action that could contribute to neurobehavioral deficits associated with the fetal alcohol syndrome. Whether these changes are due to cellular damage, delayed gene expression or post-translational modification needs to be determined.
Published Version
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