REDUCTION OF RAT PUP ULTRASONIC VOCALIZATIONS BY THE NEUROACTIVE STEROID ALLOPREGNANOLONE

Several of the recently characterized neuroactive steroids have been p roposed to have anxiolytic effects in behavioral models when subjects were tested as adults. In this experiment, the effects on infant subje cts were examined using the isolation distress model of anxiety. The p roduction of ultrasonic vocalizations in week-old rat pups after mater nal separation was assessed after ICV injections of vehicle or allopre gnanolone (1.25-5 mu g), or sham injections. Subjects were also observ ed for activity and behavioral responses and tested on three measures of sedation. Allopregnanolone caused a dose-dependent decrease in ultr asonic vocalizations, with increasing motor incoordination, ataxia, an d turning at the higher doses. Sex differences were not observed for a ny measure. These results suggest the GABA(A) receptor binding site fo r neuroactive steroids is behaviorally active in neonates as well as i n adults,and that the anxiolytic effects of the neuroactive steroids a t this site may be dissociable from their sedative effects at low dose s.