| Discriminative stimulus effects of diazepam, ketamine and their mixture: ethanol substitution patterns. | |
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MedLine Citation:
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PMID: 9832946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Y E Harrison; J A Jenkins; B A Rocha; D A Lytle; M E Jung; M W Oglesby |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Behavioural pharmacology Volume: 9 ISSN: 0955-8810 ISO Abbreviation: Behav Pharmacol Publication Date: 1998 Feb |
Date Detail:
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Created Date: 1998-12-29 Completed Date: 1998-12-29 Revised Date: 2009-07-07 |
Medline Journal Info:
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Nlm Unique ID: 9013016 Medline TA: Behav Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 31-40 Citation Subset: IM |
Affiliation:
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Department of Psychiatry, UT Southwestern Medical Center, Dallas 75235-9070, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Anxiety Agents / pharmacology* Central Nervous System Depressants / pharmacology* Diazepam / pharmacology* Discrimination (Psychology) / drug effects* Dizocilpine Maleate / pharmacology Dose-Response Relationship, Drug Ethanol / pharmacology* Excitatory Amino Acid Antagonists / pharmacology* Hypnotics and Sedatives / pharmacology Ketamine / pharmacology* Male Morphine / pharmacology Narcotics / pharmacology Pentobarbital / pharmacology Rats |
| Grant Support | |
ID/Acronym/Agency:
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AARO1-9378/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Anxiety Agents; 0/Central Nervous System Depressants; 0/Excitatory Amino Acid Antagonists; 0/Hypnotics and Sedatives; 0/Narcotics; 439-14-5/Diazepam; 57-27-2/Morphine; 64-17-5/Ethanol; 6740-88-1/Ketamine; 76-74-4/Pentobarbital; 77086-22-7/Dizocilpine Maleate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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