Discriminative stimulus properties of CGS 9896: interactions within the GABA/benzodiazepine receptor complex.

Discriminative stimulus properties of CGS 9896: interactions within the GABA/benzodiazepine receptor complex.

Leidenheimer N J; Schechter M D

Pharmacology, biochemistry, and behavior

1988

1988-10

Male rats were trained to discriminate the stimulus effects of CGS 9896 (30.0 mg/kg) from its vehicle. Once trained, discriminative performance was observed to be dose-responsive in the 3.75-30.0 mg/kg range and analysis of the dose-response curve generated an ED50 of 6.44 mg/kg. Generalization testing with chlordiazepoxide and pentobarbital produced CGS 9896-appropriate responding, whereas administration of the GABA agonists SL 75 102 resulted in 75% (intermediate) generalization to the CGS 9896 discriminative stimulus. Although full antagonism of the CGS 9896 cue was obtained following administration of Ro15-1788 and pentylenetetrazole, the inverse agonist DMCM failed to provide complete antagonism. These results suggest that the discriminative properties of CGS 9896 are consistent with its activity as a benzodiazepine receptor agonist.

Male; Animals; Rats; Pentobarbital/pharmacology; Carbolines/pharmacology; Chlordiazepoxide/pharmacology; Discrimination (Psychology)/drug effects/*physiology; Flumazenil/pharmacology; gamma-Aminobutyric Acid/analogs & derivatives/pharmacology; Pentylenetetrazole/pharmacology; Pyrazoles/antagonists & inhibitors/*metabolism; Dose-Response Relationship; Drug; Inbred Strains; Receptors; GABA-A/*physiology

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