The goal of this study was to determine if buprenorphine continues to reduce cocaine self-administration over long periods of treatment, or if tolerance develops to this effect. The effects of 30 to 120 days of buprenorphine treatment (0.32 mg/kg/day) on cocaine and food self- administration were examined in six rhesus monkeys. Saline control treatment was studied for 15 days before and after buprenorphine treatment. Intravenous cocaine (0.05 or 0.10 mg/kg) and food (1 g banana pellet) self-administration were maintained on a FR 4 (VR 16:S) schedule of reinforcement. Cocaine self- administration decreased significantly (P < .0001) and remained 60 to 97% below saline treatment baseline levels (52 ± 2 injections/day) throughout 120 days of buprenorphine treatment (P < .01). After substitution of saline for buprenorphine, cocaine self-administration resumed and averaged between 21 (±3.6) and 56 (±6.5) injections per day over 20 days. Buprenorphine plasma levels averaged 18 (±2.84) ng/ml (range 10.9-30 ng/ml) during buprenorphine treatment. Buprenorphine plasma levels usually decreased by 50% or more within 27 hr after the last buprenorphine dose. Low levels of buprenorphine (0.10-0.19 ng/ml) were measured for 30 to 74 days after abrupt termination of daily buprenorphine treatment. Food self-administration was initially reduced (P < .01-0.5), but tolerance to buprenorphine's suppression of food-maintained responding developed over 30 to 70 days of treatment. Food self-administration returned to and significantly exceeded (P < .05-.01) saline treatment base-line levels, whereas cocaine self-administration remained significantly suppressed. We conclude that daily buprenorphine administration selectively reduced cocaine self-administration, and this effect persisted for as long as 120 days. These data confirm and extend our previous reports that 15 days of buprenorphine treatment (0.237-0.70 mg/kg/day) selectively reduced cocaine self-administration by rhesus monkeys.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1992|
ASJC Scopus subject areas
- Molecular Medicine