Tolerance or sensitization to the locomotor-activating effects of cocaine occurs depending upon the treatment regimen that is used. When cocaine is injected on a daily basis, sensitization occurs, whereas continuously infused cocaine leads to tolerance. Male Sprague-Dawley rats were treated for 7 days with continuous cocaine (50 mg/kg/day) via subcutaneously implanted osmotic minipumps, after which the pumps were removed. Locomotor activity was measured for 1 h each day. Some rats were challenged with an injection of cocaine (7.5, 15 or 30 mg/kg) either 2 or 9 days after pump removal. Two days after the pumps were removed (Day 10), there were no significant differences between cocaine- or saline-treated rats in the amount of locomotor activity produced by the challenge injections. However, cocaine-treated rats challenged with cocaine 9 days after pumps were removed (Day 17) exhibited significant tolerance, as evidenced by a shift downward of the cocaine curve, as compared to saline controls. When the rats were injected again on the next day (Day 18), the activity levels of both groups increased, as compared to the effects observed on Day 17. Thus, although the cocaine-treated rats were still tolerant compared to the saline-treated rats, they were sensitized compared to their previous response to a challenge injection. These findings indicate that tolerance and sensitization to the locomotor-activating effects of cocaine can exist simultaneously, which suggests that they are mediated by separate mechanisms.
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