ULTRASONIC VOCALIZATIONS IN RAT PUPS - MODULATION AT THE GAMMA-AMINOBUTYRIC ACID(A) RECEPTOR COMPLEX AND THE NEUROSTEROID RECOGNITION SITE

Agonists acting at benzodiazepine, gamma-aminobutyric acid(A), barbitu rate and neurosteroid recognition sites were studied for their attenua tion of separation-induced ultrasonic vocalizations (USV) in rat pups. The behavioral effects of the neuroactive steroid 3 alpha-hydroxy-5 a lpha-pregnan-20-one (allopregnanolone) were assessed when the drug was administered alone and in combination with agonists and antagonists a cting at the gamma-aminobutyric acid, receptor complex. At 7 days post partum, male and female Long-Evans rat pups were separated from the da m and littermates, and placed on a 20 degrees C surface for 2 min. All opregnanolone (130 mg/kg s.c.), alprazolam (0.03-1 mg/kg s.c.), diazep am (0.13 mg/kg s.c.), muscimol (0.03-0.3 mg/kg s.c.) and pentobarbital (130 mg/kg s.c.) dose-dependently decreased USV. Pretreatment with fl umazenil (0.1 mg/kg s.c.) antagonized alprazolam's and diazepam's USV- suppressive effects; bicuculline (2 mg/kg s.c.) reversed muscimol's US V-suppressive effects. Allopregnanolone (3 mg/kg s.c.) produced a 4- t o 7-fold leftward shift in alprazolam's and diazepam's USV-suppressive effects, and also produced a modest leftward shift in pentobarbital's USV dose-effect function. Neither flumazenil, bicuculline, nor picrot oxin (1 mg/kg s.c.) altered allopregnanolone's USV-suppressive effects . These results suggest that the USV-suppressive effects of the neuros teroid allopregnanolone are mediated at the gamma-aminobutyric acid, r eceptor complex, and are independent from a direct action on the benzo diazepine or gamma-aminobutyric acid, recognition sites on this comple x.