| Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors. | |
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MedLine Citation:
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PMID: 12420154 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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RATIONALE: The discriminative stimulus effects of zolpidem in squirrel monkeys trained at doses greater than or equal to 3.0 mg/kg differ from those of conventional benzodiazepines (BZs), but the extent to which these effects reflect the selectivity of zolpidem for GABA(A)/alpha(1) receptors is not known. OBJECTIVES: The present study investigated the ability of GABA(A)/alpha(1)-preferring agonists to substitute for training doses of zolpidem greater than or equal to 3.0 mg/kg and the ability of GABA(A)/alpha(1)-preferring antagonists to block zolpidem's discriminative stimulus effects. METHODS: Squirrel monkeys were trained to discriminate intravenous injections of zolpidem (3.0 or 5.6 mg/kg) from saline and tested with BZ agonists differing in selectivity and efficacy at GABA(A)/alpha(1) receptors. Antagonism of the effects of zolpidem was studied using the GABA(A)/alpha(1)-preferring antagonists beta-carboline-3-carboxylate-t-butyl ester (beta-CCT) and 3-propyloxy-beta-carboline (3-PBC). RESULTS: Zolpidem and quazepam (GABA(A)/alpha(1)-preferring agonist) engendered full substitution for zolpidem, whereas CL 218,872 (GABA(A)/alpha(1)-preferring partial agonist) and the non-selective BZ agonists alprazolam and flunitrazepam engendered low and variable levels of zolpidem-lever responding (35-58%). Both beta-CCT and 3-PBC antagonized the discriminative stimulus effects of zolpidem in a surmountable fashion. CONCLUSIONS: Our findings provide evidence for a key role of GABA(A)/alpha(1) receptors in the discriminative stimulus effects of zolpidem at relatively high training doses, and suggest that selectivity and relatively high efficacy at GABA(A)/alpha(1) receptors is required for BZ agonists to reproduce these discriminative stimulus effects. |
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Authors:
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James K Rowlett; Roger D Spealman; Snjezana Lelas; James M Cook; Wenyuan Yin |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2002-11-06 |
Journal Detail:
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Title: Psychopharmacology Volume: 165 ISSN: 0033-3158 ISO Abbreviation: Psychopharmacology (Berl.) Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2003-01-23 Completed Date: 2003-05-07 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7608025 Medline TA: Psychopharmacology (Berl) Country: Germany |
Other Details:
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Languages: eng Pagination: 209-15 Citation Subset: IM |
Affiliation:
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Harvard Medical School, New England Regional Primate Research Center, One Pine Hill Drive, Box 9102, Southborough, MA 01772-9102, USA. james_rowlett@hms.harvard.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alprazolam
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pharmacology Animals Anti-Anxiety Agents / pharmacology Benzodiazepines* Carbolines / pharmacology Discrimination Learning / drug effects*, physiology Dose-Response Relationship, Drug Flunitrazepam / pharmacology GABA Agonists / pharmacology* GABA Antagonists / pharmacology Injections, Intravenous Male Pyridazines / pharmacology Pyridines / pharmacology* Receptors, GABA-A / agonists, physiology* Saimiri |
| Grant Support | |
ID/Acronym/Agency:
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DA11792/DA/NIDA NIH HHS; DA13591/DA/NIDA NIH HHS; MH46851/MH/NIMH NIH HHS; RR00168/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/3-propoxy-beta-carboline; 0/Anti-Anxiety Agents; 0/Carbolines; 0/GABA Agonists; 0/GABA Antagonists; 0/Pyridazines; 0/Pyridines; 0/Receptors, GABA-A; 0/alpha1 subunit, GABA-A receptor; 12794-10-4/Benzodiazepines; 1622-62-4/Flunitrazepam; 28981-97-7/Alprazolam; 36735-22-5/quazepam; 66548-69-4/CL 218872; 82626-48-0/zolpidem; 93835-05-3/tert-butyl beta-carboline-3-carboxylate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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