Document Detail


T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotine.
MedLine Citation:
PMID:  20579972     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-01
Journal Detail:
Title:  Biological psychiatry     Volume:  68     ISSN:  1873-2402     ISO Abbreviation:  Biol. Psychiatry     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0213264     Medline TA:  Biol Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  712-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Neuroscience, Merck & Co., Inc., West Point, Pennsylvania 19486, USA. jason_uslaner@merck.com
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Comment In:
Biol Psychiatry. 2010 Oct 15;68(8):687-8   [PMID:  20888456 ]

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