Landa Leos, Sulcova Alexandra, Slais Karel
Masaryk University, Faculty of Medicine, Department of Pharmacology, Brno, Czech Republic.
Neuro Endocrinol Lett. 2006 Feb-Apr;27(1-2):63-9.
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.
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.
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.
These results suggest that the activity of the endocannabinoid system is involved in the neuronal circuitry underlying the development of sensitization to methamphetamine.
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。
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。
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。
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。