| Chronic prenatal ethanol exposure (CPEE) can injure the developing brain, and may lead to the fetal alcohol syndrome (FAS). Previous studies have demonstrated that CPEE upregulates gamma-aminobutyric acid type A (GABAA) receptor expression in the cerebral cortex, and decreases functional synaptic plasticity in the hippocampus, in the adult guinea pig. This study tested the hypothesis that CPEE increases GABAA receptor expression in the hippocampus of guinea pig offspring that exhibit cognitive deficits in a spatial learning task. Timed, pregnant guinea pigs were treated with ethanol (4g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding, or water throughout gestation. GABAA receptor subunit protein expression in the hippocampus was measured at two development ages, near-term fetus and adult. In adult guinea pig offspring, CPEE impaired task acquisition in the Morris water maze, and increased time moving and speed of locomotor activity in the open field. CPEE did not change GABAA receptor subunit protein expression in the near term fetal hippocampus, but increased expression of the beta2/3 subunit of the GABAA receptor in the hippocampus of adult offspring. CPEE did not change either [3H]flunitrazepam binding or GABA potentiation of [3H]flunitrazepam binding, but decreased the efficacy of allopregnanolone potentiation of [3H]flunitrazepam binding, to hippocampal GABAA receptors in adult offspring. Correlational analysis revealed an inverse relationship between impaired performance in the water maze and the efficacy of allopregnanolone potentiation of [ 3H]flunitrazepam binding in the hippocampus. These data suggest that alterations in hippocampal GABAA receptor expression and pharmacological properties contribute to the behavioural and cognitive deficits associated with CPEE. |
