RT Journal Article
SR Electronic
T1 Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 160
OP 166
VO 227
IS 1
A1 H E Shannon
A1 S Herling
YR 1983
UL http://jpet.aspetjournals.org/content/227/1/160.abstract
AB Rats were trained to discriminate between saline and either 0.3, 1.0, 3.0 or 6.0 mg/kg of diazepam in a two-choice, discrete-trial avoidance procedure. Diazepam, chlordiazepoxide, flurazepam and pentobarbital occasioned dose-related increases in diazepam-appropriate responding in all four training dose groups. Increasing the training dose of diazepam from 0.3 to 1.0 mg/kg resulted in approximately a 3-fold shift to the right in the dose-effect curves for each of these four drugs. However, increasing the training dose to 3.0 or 6.0 mg/kg did not result in additional, concomitant shifts in these dose-effect curves. Moreover, the dose-effect curves of nine additional benzodiazepine analogs also did not differ markedly in rats trained with either 1.0 or 3.0 mg/kg of diazepam. The nonbenzodiazepines ethanol, phencyclidine, cyproheptadine and ketocyclazocine failed to produce diazepam-like discriminative stimuli in rats trained with either 0.3, 1.0 or 3.0 mg/kg of diazepam. In rats trained with 1.0 mg/kg of diazepam, Ro 11-6896, but not its inactive stereoisomer Ro 11-6893, occasioned diazepam-appropriate responding. Furthermore, the selective benzodiazepine antagonist CGS8216 blocked the effects of diazepam but not the diazepam-like effects of pentobarbital. These results demonstrate that the discriminative effects of diazepam are qualitatively similar across this 20-fold range of training doses; quantitatively, the discriminative effects of diazepam appear to reach a maximum and plateau above a training dose of 1.0 mg/kg in rats.(ABSTRACT TRUNCATED AT 250 WORDS)