Cocaine-induced locomotor activity in rats.

Rats were injected SC or IP with a dose of cocaine at 20 mg/kg twice daily or saline (2 ml/kg) for 15 consecutive doses. Horizontal (including ambulatory and repetitive activity) and ambulatory locomotor activities were assessed following the first (acute) and the 15th (chronic) injections. Total locomotor activity (area under curve, AUC) following the acute and the chronic administration of cocaine were comparable, regardless of the route of drug administration. However, the temporal patterns of activity were significantly different; the peak of locomotor activity occurred earlier (chronic vs. acute, 20 vs. 40 min after IP; 130 vs. 180 min after SC) following chronic cocaine administration. Furthermore, the peak activity was significantly higher (3-fold after IP and 50% after SC) in chronically than in acutely treated rats, providing evidence for sensitization. In contrast, activity in the late session (240-280 min after SC) was significantly lower following the chronic SC cocaine administration, providing evidence for desensitization. The absolute slope values of the ascending phase and the descending phase were significantly larger following chronic administration of cocaine than that following the acute dosing. The possibility of changes in locomotor activity with alteration of pharmacokinetics on chronic cocaine treatment is discussed.