Circadian activity rhythm in methamphetamine-treated Clock mutant mice.

It is well established that the Clock gene is essential for expressing circadian activity rhythms in mammals under constant darkness. The Clock gene product is a positive component of a molecular feedback loop which is assumed to generate the circadian rhythm. On the other hand, chronic treatment of methamphetamine (MAP) induces locomotor activity rhythm in a circadian domain, which is independent of the suprachiasmatic nucleus (SCN) and is driven by a pacemaker outside the SCN. However, it is not known whether the pacemaker outside the SCN possesses a similar molecular mechanism to that in the SCN. Here we show that MAP restores locomotor activity rhythm in arrhythmic homozygous Clock mutant (Clock/Clock) mice under constant darkness. This result indicates that the Clock mutation does not affect the MAP-induced locomotor rhythm.