Gao Z G, Cui W Y, Zhang H T, Liu C G
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, People's Republic of China.
Pharmacol Res. 1998 Aug;38(2):101-6. doi: 10.1006/phrs.1998.0337.
The present study examined the effects of nicotine on the levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid (DOPAC) in the striatum and on spontaneous locomotor activity of C57 black mice that had been treated with the neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The levels of dopamine and DOPAC in the striatum were significantly reduced 10 days after two injections of MPTP (40 mg kg-1, i.p., 24 h apart) in mice. Chronic treatment of nicotine (2.0 mg kg-1, s.c., four injections per day) did not influence the striatal content of dopamine and DOPAC, but it significantly antagonised MPTP-induced depression of dopamine. However, the chronic nicotine treatment did not significantly affect MPTP-induced depression of DOPAC. It was demonstrated that the lethal effect of MPTP was also partly protected by the chronic nicotine treatment. The chronic nicotine treatment also significantly protected MPTP-depressed spontaneous locomotor activity in mice. The results suggest that both MPTP-depressed behaviour and MPTP-induced striatal dopamine depletion in C57 black mice are partly protected by chronic nicotine treatment.
本研究考察了尼古丁对经神经毒素1-甲基-4-苯基-1,2,5,6-四氢吡啶(MPTP)处理的C57黑小鼠纹状体中多巴胺及其代谢物3,4-二羟基苯乙酸(DOPAC)水平以及自发运动活性的影响。在小鼠腹腔注射两次MPTP(40 mg/kg,间隔24小时)后10天,纹状体中多巴胺和DOPAC水平显著降低。尼古丁慢性处理(2.0 mg/kg,皮下注射,每天4次)不影响纹状体中多巴胺和DOPAC的含量,但能显著拮抗MPTP诱导的多巴胺降低。然而,尼古丁慢性处理对MPTP诱导的DOPAC降低无显著影响。结果表明,尼古丁慢性处理也能部分保护MPTP的致死效应。尼古丁慢性处理还能显著保护MPTP降低的小鼠自发运动活性。结果提示,尼古丁慢性处理可部分保护C57黑小鼠中MPTP抑制的行为和MPTP诱导的纹状体多巴胺耗竭。