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Buprenorphine self-administration by rhesus monkey

1981; Elsevier BV; Volume: 15; Issue: 2 Linguagem: Inglês

10.1016/0091-3057(81)90180-5

1873-5177

Nancy K. Mello, Mark P. Bree, Jack H. Mendelson,

Neurotransmitter Receptor Influence on Behavior

Intravenous injections of buprenorphine, a partial opiate agonist and antagonist, maintained operant responding under second order schedule control (FR 3 VR 16:S) across a dose range of 0.005 to 0.10 mg/kg/inj. A drug naive monkey and four monkeys with a history of morphine self-administration all self-administered buprenorphine at all doses studied. Four monkeys showed dose-related increases in the total amount of buprenorphine (mg/kg) self-administered each day as the available dose increased from 0.01 to 0.10 mg/kg/inj. Injections per day remained equivalent to the number of injections at the lowest dose studied or increased significantly (p<0.05, 0.01), as the dose per injection increased in three monkeys. Even at high buprenorphine doses, there was no evidence of sedation. Monkeys consistently self-administered significantly more buprenorphine than saline in control studies (p<0.01). Buprenorphine's agonistic effects appear to persist for 24 to 48 hours. When saline and buprenorphine were available on alternate days, monkeys did not distinguish between them, but when 3 days of saline were alternated with 1 day of buprenorphine (0.03 mg/kg/inj), monkeys took significantly more buprenorphine than saline (p<0.02−0.001). Abrupt discontinuation of buprenorphine (0.10 mg/kg/inj) did not result in discernible withdrawal signs. The effects of buprenorphine on food intake were inconsistent, but there were no significant changes in body weight as a function of chronic buprenorphine self-administration or withdrawal. These data indicate that buprenorphine is a positive reinforcer in rhesus monkeys and maintains behavior leading to its administration on second order schedules over a wide dose range. Despite its opiate agonist properties, there was no evidence of physical dependence.