Chronic naltrexone treatment increases the heroin-produced facilitation of self-stimulation.

The facilitatory effects of heroin HCl (0.25 mg/kg, SC) on self-stimulation (SS) of the lateral hypothalamus before and after chronic treatment of naltrexone (10 mg/kg, SC, for 20 days) or vehicle were compared. The group that received chronic naltrexone had a larger heroin-induced facilitation of SS than the group that received vehicle. These data suggest that the sensitivity to the facilitatory effect of heroin on SS may be related to the amount of opiate receptor binding which is increased following chronic antagonist treatment. However, neither acute nor chronic treatment with naltrexone produced any significant changes in SS thresholds, suggesting that the directly stimulated substrate for the rewarding effect of brain stimulation is unlikely to be endorphinergic but is apparently modulated by the endogenous opioid system.