Dose- and time-dependent effects of narcotic analgesics on intracranial self-stimulation in the rat

Rats were trained to bar-press in order to obtain electrical stimulation of the medial forebrain bundle through chronically implanted electrodes. Dose-response and time-effect curves were determined for morphine (1.0-30 mg/kg), levorphanol (0.1 to 3.0 mg/kg), methadone (0.1-3.0 mg/kg), meperidine (1.0-30 mg/kg), oxymorphone (0.03-1.0 mg/kg), and d-amphetamine (0.1-3.0 mg/kg). Dose-response and time-effect curves were also determined for morphine (1.0-30 mg/kg) in rats that had received multiple injections of morphine over a period of 3 days. All of the narcotic analgesics produced dose-related decreases in responding; the durations of these decreases were also dose-related. The relative potencies of the five narcotic analgesics with respect to the rate-decreasing effects for selt-stimulation responding were: oxymorphone greater than levorphanol greater than methadone greater than morphine greater than meperidine. In morphine-tolerant rats the rate-decreasing effects of morphine on responding for selt-stimulation were attenuated. These findings suggest that narcotic analgesics from diverse chemical families have a similar, predominantly depressant, effect on self-stimulation behavior and that the relative potencies of a series of narcotics for this effect are similar to those demonstrated for other properties of these drugs.