• J W Ternes, R N Ehrman, and C P O'Brien.
• Behav. Neurosci. 1985 Jun 1; 99 (3): 583-8.

AbstractFour monkeys, 2 rhesus and 2 cynomolgus, were trained to perform a multiple fixed-ratio extinction (MULT/FR/EXT) schedule for banana pellets. Subsequently, all animals were given hydromorphone (HYM) self-administration training, which consisted of substitution of FR (fixed ratio) 2 cocaine for FR 80 banana pellets and substitution of FR 2 HYM for FR 2 cocaine. All of the animals acquired cocaine self-administration. They also acquired HYM self-administration when it was substituted for cocaine. Next, 50 HYM self-maintenance sessions were given. During these sessions, animals were allowed to self-administer a total cumulative dose of 1 mg/kg/day of HYM. The animals were observed for spontaneous withdrawal while they performed an operant for food 24 and 48 hr after their last maintenance dose of HYM. Because none of the monkeys showed signs of spontaneous withdrawal or disruption of the appetitive baseline during the first postmaintenance appetitive session, a 0.4-mg dose of naloxone was administered noncontingently to test for precipitated withdrawal. Naloxone disrupted appetitive responding for banana pellets in the 2 rhesus monkeys. Naloxone had no effect on responding for food in the cynomolgus monkeys. Because none of the monkeys showed signs of spontaneous withdrawal or disruption of their appetitive baseline during the second postmaintenance session, a HYM challenge dose of 1 mg/kg was given noncontingently to assess whether tolerance to the daily maintenance dose had been acquired. The bolus dose of HYM suppressed lever pressing for food in both species, a result indicating a lack of tolerance. These results suggest that the positive reinforcing properties of HYM are sufficient to maintain opioid self-administration and that tolerance and physical dependence are not necessary.

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