Neurochemical studies on the interaction cocaine and alcohol

同时使用酒精和其他药物是一个严重的问题。可卡因是海外最常被滥用的毒品。人们注意到，同时使用酒精和可卡因的案例越来越多。动物的酒精偏好（AP）是人类饮酒行为的一个指标。在这项研究中，研究了脑单胺和酒精代谢，以阐明单次或多次服用可卡因后AP变化的机制。自交系小鼠给予C57BL/6J、10%酒精和自来水，经1次或多次腹腔注射可卡因1周后测定AP。测定小鼠体内血液酒精消失率（β值）和体外肝脏酒精脱氢酶（ADH）、醛脱氢酶（ALDH）活性。还测量了大脑去甲肾上腺素、多巴胺、血清素及其代谢物的变化。单次给药可降低C57BL/6J小鼠的AP。经可卡因预处理后β值无变化。服用可卡因两小时后，脑内多巴胺水平升高。在重复给药时，给药后AP降低。脑单胺水平没有改变。单次或多次给药均未改变β值和肝脏ADH、ALDH活性。推测AP的减少与脑多巴胺的增加有关，AP的变化在药理学上对酒精代谢没有贡献。多巴胺能系统在一定程度上控制了饮酒行为。

Concurrent use of alcohol and other drugs is a serious problem. Cocaine is the most frequently abused drug overseas. An increasing number of cases demonstrating concurrent use of alcohol and cocaine is being noted. Alcohol preference (AP) in animals is an index of human drinking behavior. In this study brain monoamine and alcohol metabolism were studied to clarify the mechanisms of change in AP following single or repeated cocaine administration.To inbred strain of mouse, C57BL/6J,10% alcohol and tap water were given and AP was measured following intraperitoneal cocaine administration once or repeatedly for one week. Then the rate of blood alcohol disappearance in vivo (beta value) and liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in vitro were measured. Changes in brain norepinephrine, dopamine, serotonin and their metabolites were also measured.A single cocaine administration reduced the AP of C57BL/6J mice. beta value was not changed after pretreatment with cocaine. The level of brain dopamine was increased only two hours after cocaine adiministration. In repeated cocaine administration, AP was reduced after cocaine administration. Brain monoamine levels were not changed. Neither the beta value nor liver ADH,ALDH activity was changed after either single or repeated cocaine administration.It is speculated that reduced AP is associated with an increase in brain dopamine and changes in AP did not contribute to alcohol metabolism pharmacologically. Dopaminergic system makes a rule of, in part, alcohol drinking behavior.