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Vol. 282, Issue 1, 318-325, 1997
-Aminobutyric AcidA Receptor Complex and the
Neurosteroid Recognition Site1,2
Department of Psychology, Tufts University, Medford, Massachusetts
Agonists acting at benzodiazepine,
-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 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 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
-aminobutyric acidA
receptor complex, and are independent from a direct action on the
benzodiazepine or
-aminobutyric acidA recognition sites
on this complex.
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