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Discriminative stimulus effects of diazepam, ketamine and their mixture: ethanol substitution patterns.
Behav Pharmacol. 1998 Feb; 9(1):31-40.BP

Abstract

When ethanol is used as a training stimulus in drug discrimination experiments, benzodiazepines (such as diazepam) as well as non-competitive N-methyl-D-aspartate (NMDA) antagonists (such as ketamine) substitute for ethanol; in contrast, when a benzodiazepine or an NMDA antagonist is used as a training drug, ethanol does not substitute reliably. In the present experiments, we trained rats to discriminate a mixture of diazepam and ketamine, to test the hypothesis that ethanol would substitute for this drug combination. Using a two-lever choice procedure with food as a reinforcer, 22 rats were trained to discriminate a mixture of diazepam (5.6 mg/kg) and ketamine (10 mg/kg) from vehicle. When administered as a mixture, diazepam and ketamine substituted for the training mixture in a dose-dependent manner. When administered separately, diazepam or ketamine substituted for the mixture with full substitution occurring at 5.6 and 17.8 mg/kg, respectively. Ethanol almost completely substituted for the mixture at 1 g/kg. There was no cross-substitution between diazepam and ketamine in rats trained to discriminate diazepam (5.6 mg/kg, n = 10) or ketamine (10 mg/kg, n = 12) from vehicle. In addition, ethanol did not substitute for the training drug in either of these discriminations. These results suggest that the simultaneous action of GABAA agonist and NMDA antagonist mechanisms produce a greater ethanol-specific discriminative stimulus than activation of either component individually.

Authors+Show Affiliations

Department of Psychiatry, UT Southwestern Medical Center, Dallas 75235-9070, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9832946

Citation

Harrison, Y E., et al. "Discriminative Stimulus Effects of Diazepam, Ketamine and Their Mixture: Ethanol Substitution Patterns." Behavioural Pharmacology, vol. 9, no. 1, 1998, pp. 31-40.
Harrison YE, Jenkins JA, Rocha BA, et al. Discriminative stimulus effects of diazepam, ketamine and their mixture: ethanol substitution patterns. Behav Pharmacol. 1998;9(1):31-40.
Harrison, Y. E., Jenkins, J. A., Rocha, B. A., Lytle, D. A., Jung, M. E., & Oglesby, M. W. (1998). Discriminative stimulus effects of diazepam, ketamine and their mixture: ethanol substitution patterns. Behavioural Pharmacology, 9(1), 31-40.
Harrison YE, et al. Discriminative Stimulus Effects of Diazepam, Ketamine and Their Mixture: Ethanol Substitution Patterns. Behav Pharmacol. 1998;9(1):31-40. PubMed PMID: 9832946.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus effects of diazepam, ketamine and their mixture: ethanol substitution patterns. AU - Harrison,Y E, AU - Jenkins,J A, AU - Rocha,B A, AU - Lytle,D A, AU - Jung,M E, AU - Oglesby,M W, PY - 1998/12/2/pubmed PY - 1998/12/2/medline PY - 1998/12/2/entrez SP - 31 EP - 40 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 9 IS - 1 N2 - When ethanol is used as a training stimulus in drug discrimination experiments, benzodiazepines (such as diazepam) as well as non-competitive N-methyl-D-aspartate (NMDA) antagonists (such as ketamine) substitute for ethanol; in contrast, when a benzodiazepine or an NMDA antagonist is used as a training drug, ethanol does not substitute reliably. In the present experiments, we trained rats to discriminate a mixture of diazepam and ketamine, to test the hypothesis that ethanol would substitute for this drug combination. Using a two-lever choice procedure with food as a reinforcer, 22 rats were trained to discriminate a mixture of diazepam (5.6 mg/kg) and ketamine (10 mg/kg) from vehicle. When administered as a mixture, diazepam and ketamine substituted for the training mixture in a dose-dependent manner. When administered separately, diazepam or ketamine substituted for the mixture with full substitution occurring at 5.6 and 17.8 mg/kg, respectively. Ethanol almost completely substituted for the mixture at 1 g/kg. There was no cross-substitution between diazepam and ketamine in rats trained to discriminate diazepam (5.6 mg/kg, n = 10) or ketamine (10 mg/kg, n = 12) from vehicle. In addition, ethanol did not substitute for the training drug in either of these discriminations. These results suggest that the simultaneous action of GABAA agonist and NMDA antagonist mechanisms produce a greater ethanol-specific discriminative stimulus than activation of either component individually. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/9832946/Discriminative_stimulus_effects_of_diazepam_ketamine_and_their_mixture:_ethanol_substitution_patterns_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=9832946.ui DB - PRIME DP - Unbound Medicine ER -