Behavioral effects of morphine and phencyclidine in rats: the influence of repeated testing before and after single treatment.

Morphine-induced antinociception was determined in rats by using the hot plate procedure (56 degrees C). Two responses of the animals were analysed, i.e. the lick and the jump response. Repeated pre-exposure to the hot plate procedure shortly before morphine treatment augmented the efficacy of morphine to induce antinociception as measured by the lick response but markedly decreased the efficacy of this drug to lengthen the latency of the jump response in the same rat. The ED50 for intraperitoneally injected morphine increased from 1.7 (0.7-3.9) to 9.8 (6.5-14.7) mg/kg when rats were pre-exposed to the hot plate procedure and the latency of the jump response was measured. The slope of the dose-response curve was steeper after pre-exposure. Intraperitoneal or intravenous treatment with morphine markedly increased the latency of the jump response up to 3-4 h after injection, but only when rats were exposed twice or more to the hot plate procedure in the first hour(s) after injection. The effect of morphine was even present 24 h after injection. The maintenance of the morphine-induced effect is likely to have depended on opioids, since the effect disappeared after naloxone treatment. Phencyclidine induced a dose-related increase in locomotor activity (ED50: 0.97 (0.85-1.10) mg/kg) and in circling behavior (ED50: 1.02 (0.85-1.17) mg/kg) when the rats were tested 15 min after a subcutaneous injection. The effect of phencyclidine lasted longer when the rats were tested repeatedly after drug treatment, than when the rats were tested only once. This phenomenon was due to a decrease with time of the effects measured in the placebo-treated control rats repeatedly exposed to test procedure. The results demonstrate that repeated exposure to tests of behavior before and after treatment with psychoactive drugs markedly influences the behavioral action of these drugs. This has consequences for the determination of the efficacy and the time course of action of these drugs, especially when animals are exposed repeatedly to the test procedure in the absence or presence of the drug.