Discriminative effects of phenazepam and gidazepam in rats: comparison with other GABA-related drugs.
The present study assessed the discriminative stimulus effects of phenazepam (PHZ) (2 mg/kg, i.p.), gidazepam (GDZ) (10 mg/kg, i.p.), pentobarbital (PB) (10 mg/kg, i.p.), and buspirone (B) (5 mg/kg, i.p.) by testing GABA-related drugs in the two-lever liquid reinforced operant discrimination procedure in rats. Diazepam (5-30 mg/kg, i.p.) dose dependently and completely substituted in GDZ-trained rats and in only 40% PHZ-trained rats. Following phenobarbital (40-100 mg/kg, i.p.) injections the mean percentages of PHZ- and GDZ-lever responding generally were a monotonically increasing function of dose, but peaked at 39.3 and 52.9%, respectively. The PB discriminative cue was generalized completely to PHZ, GDZ, and phenobarbital. Picrotoxin (2 mg/kg, s.c.) did not inhibit the PHZ and GDZ discriminations, while it antagonized the PB (10 mg/kg, i.p.) cue. Calcium valproate (200 mg/kg, i.p.) failed to produce PHZ effects, and partially substituted for GDZ. B failed to substitute for the discriminative effects of PHZ, GDZ, or PB, producing a maximum 9.3, 18.0, and 33.3% drug lever responding, respectively. These results suggest that the discriminative stimuli of PHZ and GDZ are similar to those of other benzodiazepine agonists. However, the PHZ cue is more selective than that of GDZ.
Kalinina
T S
TS
Institute of Pharmacology of RAMS, Moscow, Russia.
Garibova
T L
TL
Voronina
T A
TA
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002065:Buspirone / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D018757:GABA Modulators / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D017366:Serotonin Receptor Agonists; D001569:Benzodiazepines; C017928:phenazepam; D010424:Pentobarbital; D002065:Buspirone; C077010:gidazepam