Disorganization of the rat activity rhythm by chronic treatment with methamphetamine

Remarkable changes in the circadian activity rhythm of rats were observed when they were chronically treated with methamphetamine dissolved in drinking water. The circadian rhythm was phase-delayed with respect to the light-dark (LD) cycle, and showed signs of relative coordination. In some rats, the circadian organization was disturbed and two activity components appeared, with one component free-running and the other entrained by the LD cycle. After methamphetamine withdrawal, these changes disappeared rapidly but there were transient periods of 2-3 days before establishment of a stable entrainment to the LD cycle. The changes in the circadian rhythm persisted even in constant darkness (DD). The period around 24 hr in DD was significantly shorter during methamphetamine treatment than after the drug withdrawal. These results indicate that neither alteration of the sensitivity to light nor lengthening of the intrinsic period is involved in the methamphetamine induced disorganization of the circadian rhythm. Possible mechanisms are discussed in terms of a multi-oscillatory system.