The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats
The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats
复制标题
DOI：
10.1016/j.brainres.2012.01.030
复制
发表时间：
2012-03-20
期刊：
影响因子：
2.9
通讯作者：
Przegalinski, Edmund
中科院分区：
文献类型：
--
作者：
Adamczyk, Przemyslaw;Miszkiel, Joanna;Przegalinski, Edmund
有证据表明，大麻素CB 1受体的紧张性激活在可卡因寻找行为的消退/恢复中起作用，但不参与可卡因自我给药的维持。为了进一步探索其他内源性大麻素相关受体在可卡因成瘾动物模型中的重要性，本文研究了大麻素CB 2受体拮抗剂N-（（1 S）-endo-1，3，3-三甲基双环（2.2.1）庚-2-基）-5-甲基-2-（三氟甲基）苯甲酸酯（4-chloro-3-methylphenyl）-1-（4-甲基苄基）-吡唑-3-甲酰胺（SR 144528）和瞬时受体电位香草素1型（TRPV 1）受体拮抗剂N-（3-甲氧基苯基）-4-氯肉桂酰胺（SB 366791）静脉内（i. v.）大鼠可卡因自我给药和可卡因寻求行为的消退/恢复。为了比较和参考的目的，还检查了大麻素CB 1受体拮抗剂N-（哌啶-1-基）-5-（4-罗多苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺（AM 251）的作用。此外，为了比较这些药物对人工（可卡因）与天然（食物）奖励的操作性杠杆反应的影响，还评价了食物自我给药。我们的研究结果表明，AM 251（1-3 mg/kg），SR 144528（0.1-1 mg/kg）和SB 366791（0.3-1 mg/kg）不影响可卡因自我给药。然而，AM 251（0.1-1 mg/kg）、SR 144528（0.1-1 mg/kg）和S13366791（0.1-1 mg/kg）减少可卡因诱导的可卡因寻求行为的恢复，AM 251（0.3-1 mg/kg）减少线索诱导的恢复。此外，AM 251（3 mg/kg）、SR 144528（0.1-1 mg/kg）和SB 366791（0.1-1 mg/kg）轻微降低了食物自我给药行为，但仅AM 251（3 mg/kg）降低了食物奖励。总之，我们的研究结果首次表明，CB 2或TRPV 1受体的紧张性激活参与可卡因诱导的可卡因寻求行为的恢复，但它们的活性不是这种精神兴奋剂的奖励作用所必需的。与CB 1受体相反，CB 2和TRPV 1受体在线索诱导的可卡因寻求行为恢复中均不起作用。(C)2012爱思唯尔有限公司版权所有。
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-rodophenyl)-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 S13366791 (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. (C) 2012 Elsevier B.V. All rights reserved.