66, 67 Light-Induced Per expression during dawn and dusk advance and delay, respectively, the phase of clrcadlan PER accumulation, and this

keeps circadian rhythms tuned to the photoperiod.68 Under certain circumstances behavioral rhythms do not require an Intact SCN. When laboratory rodents like mice, rats, or hamsters, are offered food during a restricted time period during the day, they entrain to the imposed feeding schedule and anticipate feeding, as manifested by wheel running bouts several hours before getting access to meals. After food Is Inhibitors,research,lifescience,medical offered ad libitum again, the animals still display anticipatory behavior for a few days, indicating that the foodentrained oscillator (FEO) can free-run during a limited time span. Despite considerable Inhibitors,research,lifescience,medical efforts, the FEO has not yet been associated unequivocally with an anatomical region In the brain or elsewhere. 69 The “methamphetamine-sensltive circadian oscillator” (MASCO) is perhaps even more mysterious than the FEO. In 1987 Honma and colleagues noticed that the administration of methamphetamine in drinking water rescued Inhibitors,research,lifescience,medical behavioral rhythmlcity In SCN-lesioned rats.70 More recently, this was also demonstrated for mice.71, 72 Of note, methamphetamine also restores rhythmic locomotor activity In Clock

À19 mutant mice.73 Strikingly, chronic methamphetamine treatment of rats engenders a splitting of locomotor activity from other circadian outputs. For example, Inhibitors,research,lifescience,medical rPerl

expression In SCN neurons and NU7441 in vivo plasma melatonin rhythms are not affected by methamphetamine in rats that are kept under 12-hour light-dark cycles, but the period length of locomotor activity Is considerably lengthened In these animals.74 Moreover, rPer1, rPer2, and rBmal1 expression was found to be completely phaseInverted In the Inhibitors,research,lifescience,medical caudate-putamen and the parietal cortex of methamphetamlne-treated rats. These unexpected findings are open to speculation, but I find the following scenario worth considering: In untreated animals with an intact SCN, the MASCO-containlng brain region may be a relay center In the processing of SCN outputs to dally rest-activIty cycles. SCN lesion may lead to a desynchronizatlon of cellular oscillators In this relay station, manifesting Itself In the loss of clrcadlan Bumetanide rhythmiclty Methamphetamine may enhance crosstalk between MASCO-containing cells, perhaps by facilitating intercellular oscillator coupling via signaling through dopamine or nicotinic receptors.75, 76 Of note, dopamine has been shown to activate mltogen-activated protein kinase (MAPK) and cAMP CREB,77 both known to be Involved In the phase resetting of cellular oscillators. Once phase coherence Is reached, the MASCO may now drive locomotor activity cycles independently of the SCN.