[Discriminative stimulus properties of phenazepam and lorazepam: specificity and role of GABA A receptors].
Rats were trained to distinguish the injections of phenazepam (PZ, 2 mg/kg, i.p.) and lorazepam (LZ, 2 mg/kg, i.p.) from saline in the same dose in the two-lever liquid-reinforced operant drug-discrimination (DD) paradigm experiment. A very similar level of stimulus control was obtained in both PZ- and LZ-trained animals throughout the 14 and 19-day duration of the study, respectively, the accuracy of the appropriate lever responses being no less than 80% in both cases. The principal similarity of the dynamics of PZ-saline and LZ-saline stimulus discrimination in different operant behavior schedules, their generalization profiles and the results of cross-substitution testing are indicative of the identity of the interoceptive DD properties of PZ and LZ. The results of cross-substitution tests with phenobarbital (40-100 mg/kg, i.p.), pentobarbital (10 mg/kg, i.p.), muscimol (1 mg/kg, i.p.), calcium valproate (20 mg/kg, i.p.), and pregnanolone (2 mg/kg, i.p.) as well as the tests for antagonism with bicuculline (10 mg/kg, i.p.) and picrotoxin (2 mg/kg, i.p.) showed that the DD properties of LZ strongly depend on the functional activity of GABA receptors and to a much lesser extent on the picrotoxin-binding receptor component of the GABA-receptor complex, which is additional evidence for the principal similarity of the interoceptive effects of PZ and LZ.
Kalinina
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Voronina
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Petrianina
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D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001569:Benzodiazepines / Q000494:pharmacology*; D003216:Conditioning, Operant; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology*; D018757:GABA Modulators / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D008140:Lorazepam / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C017928:phenazepam; D008140:Lorazepam