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

Ultrasonic Vocalizations In Rat Pups: Modulation at the gamma -Aminobutyric AcidA Receptor Complex and the Neurosteroid Recognition Site1,2

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

Department of Psychology, Tufts University, Medford, Massachusetts

Agonists acting at benzodiazepine, gamma -aminobutyric acidA, 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 3alpha -hydroxy-5alpha -pregnan-20-one (allopregnanolone) were assessed when the drug was administered alone and in combination with agonists and antagonists acting at the gamma -aminobutyric acidA 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 gamma -aminobutyric acidA receptor complex, and are independent from a direct action on the benzodiazepine or gamma -aminobutyric acidA recognition sites on this complex.


Copyright © by The American Society for Pharmacology and Experimental Therapeutics



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