DIFFERENTIAL BEHAVIORAL-EFFECTS OF THE NEUROACTIVE STEROID ALLOPREGNANOLONE ON NEONATAL RATS PRENATALLY EXPOSED TO ALCOHOL

The effects of prenatal alcohol exposure on the behavioral response to the neuroactive steroid allopregnanolone (3 alpha-hydroxy-5 alpha-pre gnan-20-one) were investigated in neonatal rats. Two behaviors were as sessed: retention of an odor conditioning task and production of ultra sonic vocalizations after brief maternal separation. Subjects from one of the three prenatal conditions (lab chow, alcohol, or pair-fed) rec eived either no injection or an ICV injection of vehicle or one of thr ee doses (1.25-5.0 mu g) of allopregnanolone either 20 min prior to or immediately after training in an appetitive odor association paradigm . Retention was assessed 1 h later in a two-choice odor preference cha mber. Posttraining injections of allopregnanolone caused a dose-depend ent impairment in retention in the odor task, but there was no differe ntial sensitivity to allopregnanolone in the alcohol-exposed offspring . All pretraining injections, including the vehicle, resulted in impai rments in retention on the task, suggesting an impairment due to stres s but not due to allopregnanolone. Allopregnanolone also reduced ultra sonic vocalizations after brief maternal separation in all subjects in a second experiment, but alcohol-exposed offspring displayed a dose-d ependent shift to the right in their anxiolytic response to this neuro steroid. This decreased sensitivity suggests that prenatal alcohol exp osure may cause a decrease in the density or affinity of the GABA rece ptors involved in stress response, but not cognitive processes, at thi s age.