Abstract

The effects of buprenorphine were examined under a shock titration procedure and compared to the effects of morphine. Under this procedure shock increased every 15 sec from 0 to 2.0 mA in 30 increments. Five responses within a 15-sec shock period decreased shock intensity by one increment. Both buprenorphine and morphine increased the level at which shock was maintained without decreasing rates of responding in the presence of shock. Buprenorphine-induced increases in median shock level occurred over a 10-fold dose range and were apparent for 6 to 12 hr. Dose-effect curves for morphine and buprenorphine were shifted to the right by prior administration of diprenorphine (0.001-1.0 mg/kg), naloxone (0.001-1.0 mg/kg) and beta-funaltrexamine (1.0-16.0 mg/kg), with the dose of antagonist required to restore responding to control levels being 1 to 2 log U larger for buprenorphine than for morphine. Buprenorphine-induced increases in median shock level were also restored to control levels when naloxone (1.0 mg/kg) was administered as much as 110 min after buprenorphine. Buprenorphine was not effective in antagonizing the effects of morphine. When a dose of buprenorphine which increased median shock level was administered once daily, median shock levels returned to control level within 6 to 15 days. When the morphine dose-effect curve was then redetermined in the presence of chronic buprenorphine, it exhibited a 10-fold shift to the right.