Rats were fixed with chronically indwelling electrodes for intracrania
l stimulation (ICS) of the medial forebrain bundle of the lateral hypo
thalamus. They were trained to press a bar in a Skinner box for the IC
S. 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 characteris
tic effect of enhancing rates of pressing. With continuance of daily s
essions under the influence of cocaine, the rats received daily for 5
days a combination of isradipine and naltrexone. Doses of isradipine a
nd naltrexone were smaller than a dose of either one that might modify
pressing. The combination of isradipine and naltrexone blocked cocain
e's enhancement of pressing for ICS. The same combination of isradipin
e and naltrexone did not reduce rates of pressing for ICS when cocaine
was not given. These results indicate that a combination of isradipin
e and naltrexone is apt to be an effective pharmacological adjunct to
other treatments for cocaine abuse.