Diprenorphine and naloxone in squirrel monkeys with enhanced sensitivity to opioid antagonists

The effects of diprenorphine and naloxone were examined in squirrel monkeys responding under a multiple fixed-ratio 30, fixed-interval 5-min schedule of food presentation. Dose-response curves for diprenorphine and naloxone were determined prior to and following chronic administration of 10.0 mg/kg naloxone once daily for at least 21 days. Prior to the chronic regimen, naloxone (0.1-10.0 mg/kg) had little effect on performance. At the highest dose examined, rates of responding were decreased only slightly. Diprenorphine (0.003-0.1 mg/kg) produced dose-dependent decreases in rates of responding under both components of the multiple schedule. Subsequent to the chronic naloxone regimen, doses of both naloxone and diprenorphine produced greater decreases in rates of responding. This suggests that frequent exposure to naloxone enhances its own rate-decreasing effects as well as those of diprenorphine.