Methamphetamine‐induced, suprachiasmatic nucleus‐independent circadian rhythms of activity and mPer gene expression in the striatum of the mouse

Abstract

While the suprachiasmatic nucleus (SCN) coordinates the majority of daily rhythms, some circadian patterns of expression are controlled from outside of the SCN. These include responses to daily methamphetamine (MAP) injection, or daily restricted feeding. The mechanisms underlying these SCN‐independent circadian rhythms are unknown. A circadian oscillation in the expression of mPer1 and/or mPer2, mouse period, in the SCN is considered necessary to generate an SCN‐dependent circadian rhythm. Therefore, in this experiment, we examined the association between mPer gene expression and the MAP‐induced, SCN‐independent circadian rhythm. Acute injection of MAP caused an elevation of mPer1, mBmal1, and mNpas2 gene expression in the striatum and mPer1 in the liver. Daily MAP injection at a fixed time for 6 days shifted the rhythmic mPer1 and mPer2 expression in the striatum from a nocturnal to a diurnal rhythm, but failed to affect that in the SCN. Although lesion of the SCN ‘flattened’mPer gene oscillation in the striatum and liver, daily MAP injection caused both behavioural and mPer gene expression rhythms. Daily MAP injection at variable injection intervals (12–36 h) for 6 days, however, failed to produce mPer gene rhythm in the striatum. Daily repeated MAP signals may strengthen the oscillatory force of SCN‐independent circadian behavioural and molecular rhythms. The present results suggest that daily oscillation of mPer genes outside the SCN is closely associated with the regulation of SCN‐independent rhythms. Thus, the present experiment highlights strongly the important role of clock gene expression, in the brain, that underlies the circadian behavioural rhythm.

The Pineal Gland is Critical for Circadian Period1 Expression in the Striatum and for Circadian Cocaine Sensitization in Mice

“…Since SCN is thought to coordinate and regulate behavioral clocks in mammals, only a few studies have explored the SCN-independent rhythms of clock genes in the brain. Similar to our findings, Iijima et al (2002) observed SCN-independent mPer mRNA expression in the mouse striatum.…”

“…Even though all three mPer isoforms cycle at both the mRNA and the protein levels in the SCN, mPer1 also shows region-specific and SCN-independent expression rhythm (von Gall et al, 2001;Sun et al, 1997;Iijima et al, 2002). Since SCN is thought to coordinate and regulate behavioral clocks in mammals, only a few studies have explored the SCN-independent rhythms of clock genes in the brain.…”

Circadian genes, rhythms and the biology of mood disorders

“…NPAS2 may also function in the place of CLOCK in the SCN if the CLOCK protein is genetically disrupted (Debruyne et al, 2006). Though the central circadian pacemaker is located in the SCN, all of these genes are expressed throughout the brain and in other organs where they function as peripheral clocks that respond to nonphotic stimuli, and likely in other processes unrelated to circadian rhythms (Abe et al, 2001;Stokkan et al, 2001;Iijima et al, 2002;Granados-Fuentes et al, 2006;McDearmon et al, 2006;Mieda et al, 2006).…”

“…Furthermore, circadian gene expression outside of the SCN, in these specific regions, may contribute to their rhythmic activity. Circadian activity rhythms in rodents can be entrained to daytime methamphetamine injections, even in SCN lesioned animals (Iijima et al, 2002). This treatment shifts the expression of the period genes in striatal regions typically associated with movement control, in a manner that matches the shift in activity rhythms (Iijima et al, 2002).…”

“…Circadian activity rhythms in rodents can be entrained to daytime methamphetamine injections, even in SCN lesioned animals (Iijima et al, 2002). This treatment shifts the expression of the period genes in striatal regions typically associated with movement control, in a manner that matches the shift in activity rhythms (Iijima et al, 2002). This same shift in period gene expression does not occur in the SCN with methamphetamine treatment, thus there is a disconnect between the SCN, molecular rhythms in the striatum and locomotor activity rhythms.…”