| T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine. | |
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MedLine Citation:
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PMID: 20579972 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND: Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse. METHODS: We examined the influence of the novel, potent, and selective T-type calcium channel antagonist [2-(4-cyclopropylphenyl)-N-((1R)-1-{5-[2,2,2-trifluoroethyl]oxo}pyridine-2-yl)ethyl]acetamide] (TTA-A2) (.3, 1, or 3 mg/kg) on motivation for nicotine, as measured by nicotine self-administration on a progressive ratio (PR) schedule, and nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine delivery (n = 11 or 12 Long Evans rats/group). Furthermore, we examined the specificity of the TTA-A2 effects by characterizing its influence on PR responding for food (in the absence or presence of nicotine-potentiated responding), food- versus nicotine-induced cue-potentiated reinstatement for a response previously reinforced by food administration (n = 11 or 12 Wistar Hannover rats/group), and its ability to induce a conditioned place aversion. RESULTS: TTA-A2 dose-dependently decreased self-administration of nicotine on a PR schedule and the ability of both nicotine and a cue paired with nicotine to reinstate responding. The effects were specific for nicotine's incentive motivational properties, as TTA-A2 did not influence responding for food on a PR schedule but did attenuate the ability of nicotine to potentiate responding for food. Likewise, TTA-A2 did not alter food-induced cue-potentiated reinstatement for a response previously reinforced by food but did decrease nicotine-induced cue-potentiated reinstatement. Finally, TTA-A2 did not produce an aversive state, as indicated by a lack of ability to induce conditioned place aversion. CONCLUSIONS: These data suggest that T-type calcium channel antagonists have potential for alleviating nicotine addiction by selectively decreasing the incentive motivational properties of nicotine. |
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Authors:
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Jason M Uslaner; Joshua D Vardigan; Jason M Drott; Victor N Uebele; John J Renger; Ariel Lee; Zhaoxia Li; A D Lê; Pete H Hutson |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-01 |
Journal Detail:
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Title: Biological psychiatry Volume: 68 ISSN: 1873-2402 ISO Abbreviation: Biol. Psychiatry Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-04 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0213264 Medline TA: Biol Psychiatry Country: United States |
Other Details:
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Languages: eng Pagination: 712-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Neuroscience, Merck & Co., Inc., West Point, Pennsylvania 19486, USA. jason_uslaner@merck.com |
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| Comments/Corrections | |
Comment In:
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Biol Psychiatry. 2010 Oct 15;68(8):687-8
[PMID:
20888456
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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