Environmental determinants of enhanced sensitivity to the behavioral effects of naltrexone

Dose-effect curves for naltrexone were determined in three squirrel monkeys studied sequentially under four different schedule conditions: a schedule of shock postponement; a fixed-interval schedule of shock presentation; a fixed-ratio schedule of food presentation; and a fixed-ratio schedule of stimulus-shock termination. In general, responding under the shock-postponement or the fixed-interval schedules was decreased minimally by doses of naltrexone up to 30 mg/kg, and these effects were not altered appreciably after daily injections of naltrexone under the fixed-interval schedule. Under the fixed-ratio schedule of food presentation naltrexone (0.3 to 10 mg/kg) produced dose-related decreases in responding, and after repeated daily injections of naltrexone the dose-effect curve was shifted more than 3-fold to the left. Under the fixed-ratio schedule of stimulus-shock termination, however, this supersensitivity to naltrexone was not apparent: responding was decreased appreciably only after 17.6 mg/kg of naltrexone. When the fixed-ratio schedule of food presentation was reinstated, the supersensitivity to naltrexone observed previously under this schedule was not evident initially, but reappeared quickly in two of the monkeys. The greater rate-decreasing effects of naltrexone under the fixed-ratio schedules compared to the other schedules may reflect a dependency related to the control rate of responding. Supersensitivity to naltrexone occurred only under the fixed-ratio schedule of food presentation and could be reversed temporarily by intervening exposure to the schedule of stimulus-shock termination. These results extend earlier findings that the behavioral effects of drugs can be dependent upon both past and present environmental influences.