Evaluation of acute and sub-acute effects of cocaine by means of circadian variation in wheel-running and drinking in mice.

The effects of cocaine on wheel-running and drinking activities in mice, housed under a 12-h light-dark schedule (lighted period; 6:00-18:00 h), were investigated through long continuous observation. Cocaine (20 and 40 mg/kg, sc), administered at 11:00 h, acutely increased wheel-running and drinking, but it was followed by a sub-acute suppression of the spontaneous increment in both of these behaviors during the coming dark period (18:00-6:00 h). Such behavioral accelerating and suppressing effects of cocaine did not change throughout the whole course of administration, which was repeated five times at 3- to 5-day intervals. In addition to these findings, wheel-running and drinking spontaneously increased during the light period and decreased during the dark period on the day after the drug administration. On the other hand, the repeated administration of cocaine at 18:00 h never increased, but rather acutely suppressed both behaviors during the dark period, and no trends in the behavioral changes on the next day were clearly shown. These results suggest that the effects of cocaine on wheel-running and drinking differ depending on the time of day of the administration.