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-pregnan-20-one) were investigated in neonatal rats. Two behaviors were assessed: retention of an odor conditioning task and production of ultrasonic vocalizations after brief maternal separation. Subjects from one of the three prenatal conditions (lab chow, alcohol, or pair-fed) received either no injection or an ICV injection of vehicle or one of three doses (1.25-5.0 micrograms) 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 chamber. Posttraining injections of allopregnanolone caused a dose-dependent impairment in retention in the odor task, but there was no differential sensitivity to allopregnanolone in the alcohol-exposed offspring. All pretraining injections, including the vehicle, resulted in impairments in retention on the task, suggesting an impairment due to stress but not due to allopregnanolone. Allopregnanolone also reduced ultrasonic vocalizations after brief maternal separation in all subjects in a second experiment, but alcohol-exposed offspring displayed a dose-dependent shift to the right in their anxiolytic response to this neurosteroid. This decreased sensitivity suggests that prenatal alcohol exposure may cause a decrease in the density or affinity of the GABA receptors involved in stress response, but not cognitive processes, at this age.