Clock genes outside the suprachiasmatic nucleus involved in manifestation of locomotor activity rhythm in rats.
Chronic treatment of methamphetamine (MAP) in rats desynchronized the locomotor activity rhythm from the light-dark cycle. When the activity rhythm was completely phase-reversed with respect to a light dark-cycle, 24 h profiles were examined for the clock gene (rPer1, rPer2, rBMAL1, rClock) expressions in several brain structures by in situ hybridization, and for the pineal as well as plasma melatonin levels. In the MAP-treated rats, the rPer1 expression in the suprachiasmatic nucleus (SCN) showed a robust circadian rhythm which was essentially identical to that in the control rats. Circadian rhythms in pineal as well as plasma melatonin were not changed significantly in the MAP-treated rats. However, robust circadian rhythms in the rPer1, rPer2 and rBMAL1 expressions detected in the caudate-putamen (CPU) and parietal cortex were completely phase-reversed in the MAP-treated rats, compared with those in the control rats, indicating desynchronization from the SCN rhythm. Such desynchronization was not observed in the circadian rhythms of clock gene expression in the nucleus accumbens and cingulate cortex. The circadian rClock expression rhythm in the MAP-treated rats was not phase-reversed in the CPU and parietal cortex. These findings indicate that the locomotor activity rhythm in rats is directly driven by the pacemaker outside the SCN, in which rPer1, rPer2 and rBMAL1 in the CPU and parietal cortex are involved.
Masubuchi
S
S
Department of Physiology, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan.
Honma
S
S
Abe
H
H
Ishizaki
K
K
Namihira
M
M
Ikeda
M
M
Honma
K
K
D000818:Animals; D001683:Biological Clocks; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003001:Cloning, Molecular; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008550:Melatonin / Q000097:blood / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D014157:Transcription Factors
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; C513312:Per2 protein, mouse; C513311:Per2 protein, rat; C512645:Per3 protein, mouse; C512646:Per3 protein, rat; D056950:Period Circadian Proteins; D014157:Transcription Factors; D008694:Methamphetamine; D008550:Melatonin