烟碱对脑单胺类受体功能及基因表达的调节作用

Modulations of nicotine on functions and geneexpressions of monoamine receptor in the brain

目的 研究烟碱对多巴胺受体、肾上腺素受体、5 羟色胺受体功能及基因表达的影响。方法 (1)昆明种小鼠给予生理盐水或烟碱 (2mg/kg ,i.p .,3/日 ,10天 )。第 11日分别腹腔注射烟碱 (2mg/kg) ,阿扑吗啡 (3mg/kg) ,可乐定 (1mg/kg) ,8 OH DPAT(1mg/kg) ,记录给药前、后自主活动各 15min ;(2 )SD大鼠注射生理盐水或烟碱 (1.2mg/kg ,2 /日 ,SC ,14天 ) ,第 15天取脑作基因芯片 ,分析单胺类受体mRNA表达的改变。结果 反复给予烟碱可诱导小鼠对烟碱降低自主活动的作用产生耐受 ,在对烟碱产生耐受的小鼠上 ,多巴胺受体激动剂阿扑吗啡增加自主活动的作用增强 ;α2 肾上腺素受体和 5 HT1A受体激动剂可乐定和 8 OH DPAT抑制自发活动的作用减弱。在大鼠上 ,反复给予烟碱可增加脑多巴胺D1受体mR NA表达 ,降低多巴胺D3受体mRNA表达 ,不影响α2 肾上腺素受体、5 HT1A受体mRNA的表达。结论 反复给予烟碱诱导烟碱耐受 ,脑N受体功能失敏时 ,单胺类受体及其亚型功能或 /和受体mRNA表达发生变化。

Object To investigate the effects of chronic nicotine treatment on the functions and gene expressions of monoamine receptor. Method (1) After chronic nicotine or saline treated(2mg/kg, i.P, 3/day, 10d). On the 11th day, mice were injected nicotine(2mg/kg), apomorphine (3mg/kg), clonidine (1mg/kg), or 8-OH-DPAT(1mg/kg), i.p. respectively, and the effects of the drugs on the locomotor activities of them were recorded for 15min before and after drugs administration. (2) SD rats were given nicotine or saline (1.2mg/kg, 2/day,SC,14d). On the 15th day, the brains were taken out and the mRNA expressions of monoamine receptor were analysised with microarray. Result Repeated nicotine administration induced the tolerance to hypolocomotion caused by nicotine in mice. In nicotine -treated mice, locomotor activity was enhanced by dopamine receptor stimulant apomorphine, and the hypolocomotions induced by α 2-adrenergic receptor stimulant clonidine and 5-HT 1A receptor stimulant 8-OH-DPAT were decreased. After repeated nicotine treatment, the mRNA expression of D1 receptor was increased, but that of D3 receptor was decreased in rats. There were no differences in the mRNA expressions of α 2-adrenergic receptor,and 5-HT 1A receptor. Conclusion Chronic nicotine treatment can induce the tolerance to nicotine, and the desensitization of nicortinic acetylcholine receptor can change the functions and mRNA expressions of various monoamine receptors.