Sensitization does not develop to cocaine-induced potentiation of the antinociceptive effect of morphine.

Repeated intermittent cocaine administration produces a progressive increase (sensitization) in the motor stimulatory action of cocaine. Previous studies have shown that cocaine produces antinociception and also enhances the antinociceptive effect of opioid analgesics. The present study was designed to investigate if sensitization to these effects of cocaine develops. In the first part of the study, we determined if acute cocaine administration (3, 10, 30 mg/kg, intraperitoneal [i.p.]) increases the antinociceptive effect of morphine (5 mg/kg, subcutaneous [s.c.]) in rats using the hot plate test. Cocaine (30 mg/kg, i.p.), alone, produced a small but significant antinociceptive effect at 15 min after drug administration. When administered 15 min prior to morphine, cocaine dose-dependently enhanced the effect of morphine (5 mg/kg, s.c.) at the time (45 min post-cocaine) when cocaine by itself did not significantly change the hot plate latency. In the second part of the study, we examined if sensitization develops to cocaine-induced antinociception and its ability to increase the antinociceptive effect of morphine. Naïve rats were injected with either saline or cocaine (30 mg/kg) once daily for 3 days and tested on the hot plate apparatus either 24 h or 1 wk after the last cocaine injection. Some of the rats from each group were also tested for motor stimulation induced by cocaine (5 mg/kg, i.p.) 24 h after the hot plate test to confirm that sensitization had occurred to the motor stimulatory action of the drug. Additional rats were treated with saline or cocaine for 3 days, but neither treated with morphine nor tested on the hot plate apparatus, and tested for behavioral sensitization to the motor stimulatory action of cocaine (5 mg/kg, i.p.) 24 h or 1 wk later. Sensitization developed to the motor stimulatory effect of cocaine in both groups, regardless of morphine treatment on the prior day. Sensitization also developed to the antinociceptive effect of cocaine 24 h but not 1 wk after the last cocaine injection. No sensitization was observed in the ability of cocaine to enhance the antinociceptive effect of morphine. Overall, our data suggest that while cocaine enhanced the antinociceptive effect of morphine, sensitization did not develop to this action of cocaine.