Combined Effects of Methamphetamine and Cocaine with Alcohol on their Psychotropic Actions

本文观察了甲基苯丙胺（MAP）、可卡因（COC）和酒精对大鼠旷场行为及纹状体细胞外多巴胺（DA）和5-羟色胺（5-HT）反应的影响。观察MAP（4 mg/kg，IP）、COC（40 mg/kg，IP）、ALC（2g/kg，IP）、MAP+ALC和COC+ALC对大鼠行为学的影响。细胞外多巴胺（DA）和5-羟色胺（5-HT）的水平在自由活动的大鼠纹状体中也测量使用在体内微透析在每次挑战的药物。MAP使小鼠的运动和直立能力明显增强，刻板行为方式明显增多。COC对大鼠的运动、直立和刻板行为的增强作用也弱于MAP，而ALC对大鼠在旷场的行为无明显影响。MAP与ALC联合给药比单独给药表现出更长的兴奋和增强的兴奋，包括运动 ...更多信息 的MAP，并在饲养频率和刻板的程度减少，而共同管理的COC与ALC诱导严重失活的开放领域的行为。与其他药物治疗相比，MAP和MAP + ALC治疗后约40至60分钟达到平台的DA和5-HT水平升高更耐受。60分钟后MAP处理的DA水平增加到药物处理前水平的1400%，MAP+ALC增加到1000%，变化的差异具有统计学意义。其他药物处理引起的DA和5-HT变化不明显。MAP和MAP + ALC使纹状体5-HT水平分别增加到药物预处理前的2000%和2400%，但差异无统计学意义，而其他药物处理的纹状体5-HT水平无明显变化。但似乎与ALC联合给药更相关。由于MAP给药导致大鼠纹状体细胞外DA和5 HT含量增加，尤其是与ALC联合给药的DA含量增加，说明MAP的兴奋作用与DA和5 HT密切相关，细胞外神经传递是纹状体对DA能活性的5 HT能机制的补充作用。研究结果证实，ALC与MAP的共同给药是一种有效的药物治疗，在调节DA，特别是5 HT释放后产生神经毒性作用。少

The interactins of methamphetamine (MAP), cocaine (COC) and alcohol on open-field behavior and extracellular striatum dopamine (DA) and serotonin (5HT) responses in rats were examined. Rats were observed for their behavior including the number of locomotions and rearing, and expression of stereotypy under the influence of MAP (4mg/kg, IP), COC (40mg/kg, IP), ALC (2g/kg, IP), and MAP+ALC and COC+ALC during 60 minutes. Extracellular dopamine (DA) and serotonin (5HT) levels in the striatum of freely moving rats were also measured using in vivo micro-dialysis during each challenge of the drug. The MAP produced marked increase in locomotion and rearing and raised the manner of stereotypy. The COC also showed less enhancement of locomotion, rearing and stereotypy than those induced by MAP.The ALC had no notici-able change in behaviors oberved in the open field. Co-administration of MAP with ALC showed more prolonged and enhanced excitation including locomotion than the single administration … More of MAP,and a decrease in frequency of rearing and degree of stereotypy, whereas co-administration of COC with ALC induced severe inactivation on open field behavior. An elevation in DA and 5HT levels that plateaued approximately from 40 to 60 minutes after MAP and MAP plus ALC treatment was more tolerant compared to other drug treatment. DA levels by MAP treatment after 60 minutes were increased to 1400% of pre-levels of drug treatment, and were increased to 1000% by MAP+ALC,the difference of alteration being statistically significant. Variations of DA and 5HT induced by other drug treatments were not significant. 5HT levels were increased to 2000% of pre-levels of drug-pretreated striatum by MAP and 2400% by MAP plus ALC,the difference of alteration being statistically not significant, whereas those in the striatum treated by other drugs showed no significant alteration.Thus, MAP-induced psychostimulant behaviors concurrently and significantly increased, but appeared to be more relative with the co-administration of ALC.Since administration of MAP caused enhancement of both extracellular DA and 5HT contents in rat's striatum, in particular for the DA content by co-administration with ALC,indicating that excitatory effects of MAP in strongly associated with both DA and 5HT.Extracellular neurotransimission is the striatum supports the supplementary function of 5HT-ergic mechanism with DA-ergic activity. The findings confirm that co-administration of ALC with MAP is a potent drug treatment to produce neurotoxic effects following the regulation of DA,in particular, 5HT release. Less