ALTERED STRESSOR-INDUCED CHANGES IN GABA-A RECEPTOR FUNCTION IN THE CEREBRAL-CORTEX OF ADULT-RATS EXPOSED INUTERO TO DIAZEPAM

Prenatal administration of the anxiolytic drug diazepam (DZP), 2.5 mg/kg) to the pregnant rat over gestational days 14-20 altered function and stressor-induced responsiveness of the GABA(A) receptor in the cerebral cortex of exposed animals as adults. In Experiment 1, the impact of 15 min of restraint on chloride-facilitated benzodiazepine binding was evaluated in male and female rats at 70-90 days of age. Early exposure to DZP led to an enhanced potency of chloride on binding in both males and females. In Experiment 2, GABA stimulation of chloride-36 uptake was measured in male rats at 35 or 70 days of age following 10 min of forced swimming at ambient temperature. In control animals, stressor-induced changes in receptor function were not evident until 70 days, and in DZP-exposed rats the stressor had no effect on receptor function at either age. These changes in GABA(A) receptor responsiveness induced by early exposure to DZP may underlie the disrupted behavioral responses to environmental challenge that have been previously reported.