Reduction of rat pup ultrasonic vocalizations by the neuroactive steroid allopregnanolone

Several of the recently characterized neuroactive steroids have been proposed to have anxiolytic effects in behavioral models when subjects were tested as adults. In this experiment, the effects on infant subjects were examined using the isolation distress model of anxiety. The production of ultrasonic vocalizations in week-old rat pups after maternal separation was assessed after ICV injections of vehicle or allopregnanolone (1.25-5 micrograms), or sham injections. Subjects were also observed for activity and behavioral responses and tested on three measures of sedation. Allopregnanolone caused a dose-dependent decrease in ultrasonic vocalizations, with increasing motor incoordination, ataxia, and turning at the higher doses. Sex differences were not observed for any measure. These results suggest the GABAA receptor binding site for neuroactive steroids is behaviorally active in neonates as well as in adults, and that the anxiolytic effects of the neuroactive steroids at this site may be dissociable from their sedative effects at low doses.