DOSE-DEPENDENT AND AGE-DEPENDENT EFFECTS OF PRENATAL ETHANOL EXPOSUREON HIPPOCAMPAL METABOTROPIC-GLUTAMATE RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS

Prenatal ethanol exposure reduces the density of the N-methyl-D-aspart ate (NMDA) receptor agonist binding sites and decreases the capacity t o elicit long-term potentiation (LTP) in hippocampal formation of 45-d ay-old rat offspring. We hypothesized that prenatal ethanol exposure w ould reduce metabotropic-glutamate receptor (mGluR)-activated phosphoi nositide hydrolysis also. Sprague-Dawley rat dams were fed a liquid di et containing either 3.35% (v/v) ethanol or 5.0% ethanol throughout ge station. Control groups were pair-fed either isocalorically matched 0% ethanol liquid diets or lab chow ad libitum. (1S,3R)-1-aminocyclopent ane-1,3-dicarboxylic acid (trans-ACPD) stimulated inositol-1-phosphate (IP1) accumulation via activation of the mGluR in offspring whose mot hers consumed the 3.35% ethanol liquid diet was not different compared with the control groups. Furthermore, trans-ACPD stimulated IP1 accum ulation in 10- to 13-day-old offspring of the 5.0% ethanol diet group was not different compared with the control groups. However, trans-ACP D stimulated IP1 accumulation was reduced significantly in 56- to 82-d ay-old offspring of dams fed the 5.0% ethanol liquid diet compared wit h the control groups. In contrast, bethanechol stimulated IP1 accumula tion, mediated via activation of muscarinic cholinergic receptors, was not affected by maternal consumption of either ethanol liquid diet. T hese results suggest both dose- and age-dependent effects of prenatal ethanol exposure on hippocampal responsiveness to trans-ACPD-activated phosphoinositide hydrolysis. Furthermore, the ability of the 3.35% et hanol diet to alter hippocampal NMDA receptors without altering the mG luR response suggests a differential sensitivity to the effects of eth anol exposure in utero among hippocampal glutamate receptor subtypes. Recent studies indicate that activation of mGluRs facilitates NMDA rec eptor-dependent LTP. Thus, higher blood ethanol concentrations achieve d by consumption of the 5.0% ethanol liquid diet adversely affects an additional glutamate receptor mechanism associated with LTP. This addi tional effect may lead to an even greater impact of prenatal ethanol e xposure on LTP than occurs when NMDA receptor function alone is affect ed by maternal consumption of more moderate quantities of ethanol.