Effects of administering cocaine at the same versus varying times of day on circadian activity patterns and sensitization in rats

The effects of different schedules of cocaine administration on circadian activity patterns and locomotor sensitization were studied. Rats received intraperitoneal injections of either saline or 20 mg/kg cocaine at either 24- or 33-hr intervals for 8 cycles (development). After a 2-day withdrawal, they were given a cocaine challenge in a novel environment. Rats given cocaine at 24-hr intervals were hypoactive 4 to 9 hr postinjection during development and, during cocaine challenge, showed sensitization of locomotor activity. Rats given cocaine at 33-hr intervals did not show these effects. On the 33-hr-period schedule, activity was enhanced beginning 24 hr after drug receipt. Different intermittent schedules of cocaine receipt may alter the vulnerability to cocaine, and altered vulnerability may be more likely when a subsequent cocaine injection interacts with a distal state of sensitivity produced by a prior injection.