ISRADIPINE COMBINED WITH NALTREXONE PERSISTENTLY REDUCES THE REWARD-RELEVANT EFFECTS OF COCAINE AND ALCOHOL

Previous studies have revealed that the combination of small doses of isradipine and naltrexone (ISR&NTX) blocks the ability of cocaine to e nhance pressing for rewarding, lateral hypothalamic brain stimulation. Further, such combinations also reduce rats' intakes of alcoholic bev erages. Here, we asked whether ISR&NTX would lose its ability to reduc e the reinforcing effects of cocaine and alcohol when given daily. Spe cifically, 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 recei ve daily injections for another 3 weeks. During this time, they were g iven access to water and an alcoholic beverage for 2 h a day. As expec ted, placebo controls gradually increased their daily intakes until th ey were taking about 2 g/kg of ethanol daily. ISR, NTX, and ISR&NTX bl ocked the typical pattern of intakes. At the end of the 3-week period, the rats had received 80 consecutive daily injections. The data sugge st that the salient effects of ISR&NTX do not wane. The data support t he idea that ISR&NTX would be a useful pharmacotherapy for poly drug a buse. (C) 1998 Elsevier Science Inc.