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 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.