The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats

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• 作者：Przemysł ; aw Adamczyk^a ; ^{adamczyk@if-pan.krakow.pl} ; Joanna Miszkiel^a ; Andrew C. McCreary^b ; ¹ ; Mał ; gorzata Filip^a ; Mariusz Papp^c ; Edmund Przegaliń ; ski^a
• 关键词：Cocaine self-administration ; Reinstatement ; Endocannabinoid system ; Cannabinoid CB1 receptor ; Cannabinoid CB2 receptor ; Vanilloid TRPV1 receptor ; Rat
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：20 March, 2012
• 卷：1444
• 期：Complete
• 页码：45-54
• 文件大小：373 K

摘要

There is evidence that indicates that tonic activation of cannabinoid CB1 receptors plays a role in extinction/reinstatement of cocaine seeking-behavior but is not involved in the maintenance of cocaine self-administration. To further explore the importance of other endocannabinoid-related receptors in an animal model of cocaine addiction, the present paper examines cannabinoid CB2 receptor antagonist N-((1S)-endo-1,3,3-trimethylbicyclo(2.2.1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and the transient receptor potential vanilloid type-1 (TRPV1) receptor antagonist N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) on intravenous (i.v.) cocaine self-administration and extinction/reinstatement of cocaine-seeking behavior in rats. For comparison and reference purposes, the effect of the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) was also examined. Moreover, for comparison effects of those drugs on operant lever responding for artificial (cocaine) vs. natural (food) reward, food self-administration was also evaluated. Our findings show that AM251 (1-3 mg/kg), SR144528 (0.1-1 mg/kg) and SB366791 (0.3-1 mg/kg) did not affect cocaine self-administration. However, AM251 (0.1-1 mg/kg), SR144528 (0.1-1 mg/kg) and SB366791 (0.1-1 mg/kg) decreased cocaine-induced reinstatement of cocaine-seeking behavior, and AM251 (0.3-1 mg/kg) decreased cue-induced reinstatement. Moreover, AM251 (3 mg/kg), SR144528 (0.1-1 mg/kg) and SB366791 (0.1-1 mg/kg) slightly decreased food self-administration behavior, but only AM251 (3 mg/kg) reduced food reward. In conclusion, our results indicate for the first time, that tonic activation of CB2 or TRPV1 receptors is involved in cocaine-induced reinstatement of cocaine-seeking behavior, but their activity is not necessary for the rewarding effect of this psychostimulant. In contrast to CB1 receptors, neither CB2 nor TRPV1 receptors play a role in cue-induced reinstatement of cocaine-seeking behavior.