The Clock Gene Rev-Erbα Regulates Methamphetamine Actions on Circadian Timekeeping in the Mouse Brain
The circadian system in mammals consists of the central clock in the hypothalamic suprachiasmatic nucleus (SCN) and the peripheral clocks in a variety of tissues and organs. The SCN clock entrains to a light-dark cycle and resets the peripheral clocks. In addition, there are at least two other clocks in the circadian domain which are independent of the SCN and which entrain to nonphotic time cues: methamphetamine (MAP)-induced and restricted daily feeding (RF)-induced clocks. Neither the site nor the mechanism of SCN-independent clocks is known. Canonical clock genes for circadian oscillation are not required for the expression of either SCN-independent rhythm. The central catecholaminergic system is probably involved in the expression of the SCN-independent rhythms, especially of the MAP-induced rhythm. MAP-induced activity rhythms in rats and the sleep-wake cycles in humans share unique phenomena such as spontaneous internal desynchronization, circabidian rhythm and nonphotic entrainment, suggesting overlapping oscillatory mechanisms. The SCN-independent clock is an adaptation that regulates behavior in response to nonphotic time cues, and seems to be closely related to the arousal mechanism.