Isradipine in combination with naltrexone as a medicine for treating cocaine abuse

Rats were fixed with chronically indwelling electrodes for intracranial stimulation (ICS) of the medial forebrain bundle of the lateral hypothalamus. They were trained to press a bar in a Skinner box for the ICS. After stable rates of pressing for both a low and a high intensity of ICS were achieved during daily sessions, the rats were given doses of cocaine before the daily sessions. Cocaine produced its characteristic effect of enhancing rates of pressing. With continuance of daily sessions under the influence of cocaine, the rats received daily for 5 days a combination of isradipine and naltrexone. Doses of isradipine and naltrexone were smaller than a dose of either one that might modify pressing. The combination of isradipine and naltrexone blocked cocaine's enhancement of pressing for ICS. The same combination of isradipine and naltrexone did not reduce rates of pressing for ICS when cocaine was not given. These results indicate that a combination of isradipine and naltrexone is apt to be an effective pharmacological adjunct to other treatments for cocaine abuse.