Cramer C M, Gardell L R, Boedeker K L, Harris J R, Hubbell C L, Reid L D
Laboratory for Psychopharmacology, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.
Pharmacol Biochem Behav. 1998 Jun;60(2):345-56. doi: 10.1016/s0091-3057(97)00593-5.
Previous studies have revealed that the combination of small doses of isradipine and naltrexone (ISR&NTX) blocks the ability of cocaine to enhance pressing for rewarding, lateral hypothalamic brain stimulation. Further, such combinations also reduce rats' intakes of alcoholic beverages. Here, we asked whether ISR&NTX would lose its ability to reduce the reinforcing effects of cocaine and alcohol when given daily. Specifically, after almost 2 months of daily injections, ISR&NTX blocked the expression of a cocaine-induced conditioned place preference (CPP). By themselves, ISR and NTX were not effective at blocking cocaine's effects. Subsequent to the CPP procedures, the rats continued to receive daily injections for another 3 weeks. During this time, they were given access to water and an alcoholic beverage for 2 h a day. As expected, placebo controls gradually increased their daily intakes until they were taking about 2 g/kg of ethanol daily. ISR, NTX, and ISR&NTX blocked the typical pattern of intakes. At the end of the 3-week period, the rats had received 80 consecutive daily injections. The data suggest that the salient effects of ISR&NTX do not wane. The data support the idea that ISR&NTX would be a useful pharmacotherapy for poly drug abuse.
先前的研究表明，小剂量的伊拉地平与纳曲酮联合使用（ISR&NTX）可阻断可卡因增强奖赏性按压、下丘脑外侧脑刺激的能力。此外，这种联合用药还能减少大鼠酒精饮料的摄入量。在此，我们探究了ISR&NTX每日给药时是否会失去降低可卡因和酒精强化作用的能力。具体而言，在每日注射近2个月后，ISR&NTX阻断了可卡因诱导的条件性位置偏爱（CPP）的表达。单独使用时，伊拉地平和纳曲酮无法有效阻断可卡因的作用。在CPP实验之后，大鼠继续每日注射3周。在此期间，它们每天有2小时可获取水和酒精饮料。正如预期的那样，安慰剂对照组的每日摄入量逐渐增加，直至每天摄入约2 g/kg乙醇。伊拉地平、纳曲酮和ISR&NTX均阻断了典型的摄入模式。在3周实验期结束时，大鼠已连续接受80天的每日注射。数据表明，ISR&NTX的显著效果并未减弱。这些数据支持了ISR&NTX可作为多药滥用有效药物疗法的观点。
