Sa. Queen et al., DOSE-DEPENDENT AND AGE-DEPENDENT EFFECTS OF PRENATAL ETHANOL EXPOSUREON HIPPOCAMPAL METABOTROPIC-GLUTAMATE RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS, Alcoholism, clinical and experimental research, 17(4), 1993, pp. 887-893
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.