TY - JOUR T1 - Ultrasonic Vocalizations In Rat Pups: Modulation at the γ-Aminobutyric Acid<sub>A</sub> Receptor Complex and the Neurosteroid Recognition Site <sup>,</sup> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 318 LP - 325 VL - 282 IS - 1 AU - Jeffrey A. Vivian AU - Helena M. T. Barros AU - Andre Manitiu AU - Klaus A. Miczek Y1 - 1997/07/01 UR - http://jpet.aspetjournals.org/content/282/1/318.abstract N2 - Agonists acting at benzodiazepine, γ-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 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) were assessed when the drug was administered alone and in combination with agonists and antagonists acting at the γ-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 γ-aminobutyric acidAreceptor complex, and are independent from a direct action on the benzodiazepine or γ-aminobutyric acidA recognition sites on this complex. The American Society for Pharmacology and Experimental Therapeutics ER -