Mansbach R S, Balster R L
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Drug Alcohol Depend. 1993 Jan;31(2):183-91. doi: 10.1016/0376-8716(93)90071-w.
The effects of mazindol, cocaine and D-amphetamine were studied in rhesus monkeys trained to self-administer cocaine, and in rats and squirrel monkeys trained to discriminate cocaine from saline. Non-contingent intravenous drug injections were administered to monkeys responding under a session consisting of a 5-min period during which lever-pressing produced food reinforcement and a 60-min session in which responding produced i.v. cocaine infusions (10 or 33 micrograms/kg per infusion). Acute i.v. injections of cocaine (0.1-1.7 mg/kg), D-amphetamine (0.1-1 mg/kg) and the dopamine re-uptake inhibitor mazindol (0.03-0.56 mg/kg) given 5 min before the session decreased self-administration of cocaine, but also decreased rates of behavior maintained by the presentation of food. In both rats and squirrel monkeys trained to discriminate cocaine from saline in a two-lever, food-maintained procedure, mazindol, cocaine and D-amphetamine substituted for cocaine in a dose-related manner. Despite a lack of selectivity to decrease cocaine self-administration as compared to behavior maintained by food, the present data provide some rationale for further consideration of mazindol as a potential pharmacotherapy for stimulant abuse, due to its relatively low abuse liability and cocaine-like discriminative stimulus effects.
在经过训练可自行注射可卡因的恒河猴，以及经过训练能在可卡因和生理盐水之间进行辨别反应的大鼠和松鼠猴身上，研究了马吲哚、可卡因和右旋苯丙胺的作用。对在一个实验环节中做出反应的猴子进行非条件静脉注射药物，该实验环节包括一个5分钟的时段，期间按压杠杆可获得食物强化，以及一个60分钟的时段，期间做出反应可获得静脉注射可卡因（每次注射10或33微克/千克）。在实验开始前5分钟进行急性静脉注射可卡因（0.1 - 1.7毫克/千克）、右旋苯丙胺（0.1 - 1毫克/千克）以及多巴胺再摄取抑制剂马吲哚（0.03 - 0.56毫克/千克），可减少可卡因的自行注射量，但也会降低由食物呈现所维持的行为速率。在经过训练能在双杠杆、食物维持的实验程序中区分可卡因和生理盐水的大鼠和松鼠猴身上，马吲哚、可卡因和右旋苯丙胺均以剂量相关的方式替代了可卡因。尽管与由食物维持的行为相比，马吲哚在降低可卡因自行注射量方面缺乏选择性，但鉴于其相对较低的滥用可能性以及类似可卡因的辨别性刺激效应，本研究数据为进一步考虑将马吲哚作为治疗兴奋剂滥用的潜在药物疗法提供了一些依据。
