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

研究了甲基苯丙胺（MAP）、可卡因（COC）和酒精对大鼠开场行为和细胞外纹状体多巴胺（DA）和血清素（5HT）反应的相互作用。观察60分钟内MAP （4mg/kg， IP）、COC （40mg/kg， IP）、ALC （2g/kg， IP）、MAP+ALC和COC+ALC影响下大鼠的行为，包括运动次数、饲养次数、刻板印象表达。在每次给药期间，用体内微透析法测定自由活动大鼠纹状体细胞外多巴胺（DA）和血清素（5HT）水平。MAP显著增加了运动和饲养能力，提高了刻板印象的方式。与MAP相比，COC对运动、饲养和刻板印象的增强作用也较弱。ALC在开放环境中没有明显的行为变化。与单独给药相比，MAP和ALC联合给药能延长和增强小鼠的运动兴奋时间，并能降低小鼠的饲养频率和刻板印象程度，而COC和ALC联合给药则能导致小鼠在开阔场地行为上的严重失活。与其他药物治疗相比，MAP和MAP + ALC治疗后约40 - 60分钟内DA和5HT水平升高趋于稳定。MAP治疗60min后DA水平提高至药物治疗前水平的1400%，MAP+ALC治疗60min后DA水平提高至药物治疗前水平的1000%，变化差异有统计学意义。其他药物处理诱导的DA和5HT变化不显著。MAP组和MAP + ALC组分别使5HT水平提高到药物预处理纹状体前水平的2000%和2400%，差异无统计学意义，而其他药物组纹状体无显著变化。因此，map诱导的精神兴奋剂行为同时显著增加，但似乎与ALC的联合使用更相关。由于MAP的给药引起大鼠纹状体细胞外DA和5HT含量的增加，特别是与ALC共给药时，DA含量的增加，表明MAP的兴奋作用与DA和5HT都有很强的相关性。细胞外神经传递是纹状体支持5ht能与da能活性互补的机制。研究结果证实，ALC与MAP合用是一种有效的药物治疗，可在DA（特别是5HT）释放调节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