Vol. 282, Issue 1, 318-325, 1997

Ultrasonic Vocalizations In Rat Pups: Modulation at the -Aminobutyric Acid_A Receptor Complex and the Neurosteroid Recognition Site^1,2

Jeffrey A. Vivian³, Helena M. T. Barros⁴, Andre Manitiu and Klaus A. Miczek

Department of Psychology, Tufts University, Medford, Massachusetts

Agonists acting at benzodiazepine, -aminobutyric acid_A, barbiturate and neurosteroid recognition sites were studied for their attenuation of separation-induced ultrasonic vocalizations (USV) in rat pups. The behavioral effects of the neuroactive steroid 3-hydroxy-5-pregnan-20-one (allopregnanolone) were assessed when the drug was administered alone and in combination with agonists and antagonists acting at the -aminobutyric acid_A receptor complex. At 7 days postpartum, male and female Long-Evans rat pups were separated from the dam and littermates, and placed on a 20°C surface for 2 min. Allopregnanolone (1-30 mg/kg s.c.), alprazolam (0.03-1 mg/kg s.c.), diazepam (0.1-3 mg/kg s.c.), muscimol (0.03-0.3 mg/kg s.c.) and pentobarbital (1-30 mg/kg s.c.) dose-dependently decreased USV. Pretreatment with flumazenil (0.1 mg/kg s.c.) antagonized alprazolam's and diazepam's USV-suppressive effects; bicuculline (2 mg/kg s.c.) reversed muscimol's USV-suppressive effects. Allopregnanolone (3 mg/kg s.c.) produced a 4- to 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 picrotoxin (1 mg/kg s.c.) altered allopregnanolone's USV-suppressive effects. These results suggest that the USV-suppressive effects of the neurosteroid allopregnanolone are mediated at the -aminobutyric acid_A receptor complex, and are independent from a direct action on the benzodiazepine or -aminobutyric acid_A recognition sites on this complex.