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大麻素CB1和CB2受体活性在小鼠对甲基苯丙胺作用产生行为敏化过程中的参与情况。

Involvement of cannabinoid CB1 and CB2 receptor activity in the development of behavioural sensitization to methamphetamine effects in mice.

作者信息

Landa Leos, Sulcova Alexandra, Slais Karel

机构信息

Masaryk University, Faculty of Medicine, Department of Pharmacology, Brno, Czech Republic.

出版信息

Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):63-9.

Abstract

OBJECTIVES

An increased behavioural response ("behavioural sensitization") to drugs of abuse occurs after repeated treatment. In the present study the possibility of cross-sensitization existence between various cannabinoid receptor ligands--CB1 agonist methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM 251 with methamphetamine was explored.

METHODS

Locomotion in the open field was measured in naive mice and in those pre-treated acutely and repeatedly (for 8 days), respectively, with either vehicle or tested drugs.

RESULTS

Methamphetamine produced significant sensitization to its stimulatory effect on locomotion. Methanandamide pre-treatment elicited cross-sensitization to methamphetamine effect, whereas pre-treatment with JWH 015 did not. Combined pre-treatment with methamphetamine+AM 251 suppressed sensitization to methamphetamine.

CONCLUSIONS

These results suggest that the activity of the endocannabinoid system is involved in the neuronal circuitry underlying the development of sensitization to methamphetamine.

摘要

目的

反复给药后,对滥用药物的行为反应(“行为敏化”)会增强。在本研究中,探讨了各种大麻素受体配体——CB1激动剂甲磺酰胺、CB2激动剂JWH 015和CB1拮抗剂AM 251与甲基苯丙胺之间存在交叉敏化的可能性。

方法

分别在未处理的小鼠以及急性和反复(8天)预处理过的小鼠中,用溶剂或受试药物处理后,测量其在旷场中的运动能力。

结果

甲基苯丙胺对其运动刺激作用产生了显著的敏化。甲磺酰胺预处理引发了对甲基苯丙胺作用的交叉敏化,而JWH 015预处理则未引发。甲基苯丙胺与AM 251联合预处理可抑制对甲基苯丙胺的敏化。

结论

这些结果表明,内源性大麻素系统的活性参与了对甲基苯丙胺敏化发展的神经回路。

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