The effects of chronic buprenorphine treatment on cocaine and food self-administration by rhesus monkeys.
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 less than .0001) and remained 60 to 97% below saline treatment baseline levels (52 +/- 2 injections/day) throughout 120 days of buprenorphine treatment (P less than .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 less than .01-.05), 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 less than .05-.01) saline treatment base-line levels, whereas cocaine self-administration remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Mello
N K
NK
Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, Massachusetts.
Lukas
S E
SE
Kamien
J B
JB
Mendelson
J H
JH
Drieze
J
J
Cone
E J
EJ
D000818:Animals; D002047:Buprenorphine / Q000097:blood / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D004361:Drug Tolerance; D005260:Female; D005502:Food; D008253:Macaca mulatta; D008297:Male; D012646:Self Administration
D002047:Buprenorphine; D003042:Cocaine