P物质中枢给药对慢性酒精中毒大鼠乙醇摄入量影响的机制

Mechanisms of the influences of the central administration of substance P on ethanol consumption in chronically alcoholic rats.

作者信息

Nikolaev S V, Bychkov E R, Lebedev A A, Dambinova S A

机构信息

Institute of the Human Brain, Russian Academy of Sciences, 12a Academician Pavlov Street, 197376 St. Petersburg, Russia.

出版信息

Neurosci Behav Physiol. 2003 Nov;33(9):905-9. doi: 10.1023/a:1025905023554.

DOI:10.1023/a:1025905023554

PMID:14969430

Abstract

The effects of central administration of substance P (SP) on alcohol consumption and dopamine metabolism in the projections of the mesocorticolimbic and nigrostriatal systems of the brain were studied in chronically alcoholic rats. Rats received 15% ethanol solution for 6 months without choice. Intraventricular administration of SP (1 microg/rat) decreased consumption of 10% ethanol solution by 41% compared with controls in an alcohol free choice test lasting one day. After chronic alcoholism, there was a decrease in the ratio of dihydroxyphenylacetic acid (DOPA) and homovanillic acid (HVA) to dopamine in the nucleus accumbens and striatum in rats subjected to alcoholism, as compared with intact controls. Chronically alcoholic rats treated with SP showed increases in DOPA, HVA, and the DOPA:dopamine and HVA:dopamine ratios in the nucleus accumbens as compared with animals given physiological saline, by 17%, 23%, 9% and 19% respectively. The only increases in the striatum were in the absolute levels of DOPA and HVA, by 28% and 29%, while the ratios of these metabolites to dopamine remained unchanged. Thus, central administration of SP decreased the voluntary consumption of ethanol in the ethanol free choice test and enhanced dopamine metabolism in structures of the mesolimbic and nigrostriatal systems in chronically alcoholic rats.

摘要

在慢性酒精中毒大鼠中，研究了脑室内注射P物质（SP）对大脑中脑皮质边缘系统和黑质纹状体系统投射中酒精消耗及多巴胺代谢的影响。大鼠无选择地接受15%乙醇溶液6个月。在为期一天的无酒精选择试验中，脑室内注射SP（1微克/只大鼠）使10%乙醇溶液的消耗量比对照组减少了41%。与正常对照组相比，慢性酒精中毒大鼠伏隔核和纹状体中，二羟基苯乙酸（DOPA）和高香草酸（HVA）与多巴胺的比例降低。与给予生理盐水的动物相比，用SP治疗的慢性酒精中毒大鼠伏隔核中DOPA、HVA以及DOPA:多巴胺和HVA:多巴胺的比例分别增加了17%、23%、9%和19%。纹状体中仅DOPA和HVA的绝对水平增加，分别增加了28%和29%，而这些代谢产物与多巴胺的比例保持不变。因此，在无酒精选择试验中，脑室内注射SP降低了乙醇的自愿消耗量，并增强了慢性酒精中毒大鼠中脑边缘系统和黑质纹状体系统结构中的多巴胺代谢。