- 作者：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
- 关键词：Addiction ; drug abuse ; incentive salience ; progressive ratio ; relapse ; self-administration
- 刊名：Biological Psychiatry
- 出版年：2010
- 出版时间：15 October 2010
- 年：2010
- 卷：68
- 期：8
- 页码：712-718
- 全文大小：281 K
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.