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Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect.
J Pharmacol Exp Ther. 1983 Oct; 227(1):160-6.JP

Abstract

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)

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

6137554

Citation

Shannon, H E., and S Herling. "Discriminative Stimulus Effects of Diazepam in Rats: Evidence for a Maximal Effect." The Journal of Pharmacology and Experimental Therapeutics, vol. 227, no. 1, 1983, pp. 160-6.
Shannon HE, Herling S. Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect. J Pharmacol Exp Ther. 1983;227(1):160-6.
Shannon, H. E., & Herling, S. (1983). Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect. The Journal of Pharmacology and Experimental Therapeutics, 227(1), 160-6.
Shannon HE, Herling S. Discriminative Stimulus Effects of Diazepam in Rats: Evidence for a Maximal Effect. J Pharmacol Exp Ther. 1983;227(1):160-6. PubMed PMID: 6137554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect. AU - Shannon,H E, AU - Herling,S, PY - 1983/10/1/pubmed PY - 1983/10/1/medline PY - 1983/10/1/entrez SP - 160 EP - 6 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 227 IS - 1 N2 - 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) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/6137554/Discriminative_stimulus_effects_of_diazepam_in_rats:_evidence_for_a_maximal_effect_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=6137554 DB - PRIME DP - Unbound Medicine ER -