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Circasemidian, circadian, and longer-period activity rhythms in caffeine-treated molecular clock deficient cryptochrome (Cry) 1 and Cry 2 double knockout mice
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  • Satoru Masubuchi,
  • Takako Yano,
  • Kouji Komatsu,
  • Keisuke Ikegami,
  • Takeshi Todo,
  • Wataru Nakamura
Satoru Masubuchi
Aichi Medical University Graduate School of Medicine School of Medicine

Corresponding Author:[email protected]

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Takako Yano
Aichi Medical University Graduate School of Medicine School of Medicine
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Kouji Komatsu
Aichi Medical University Graduate School of Medicine School of Medicine
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Keisuke Ikegami
Aichi Medical University Graduate School of Medicine School of Medicine
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Takeshi Todo
Osaka University School of Medicine Graduate School of Medicine
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Wataru Nakamura
Nagasaki University Graduate School of Biomedical Sciences
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Abstract

Mammalian circadian rhythms are driven by the transcriptional-translational feedback loop of clock genes in the hypothalamic suprachiasmatic nucleus. However, chronic methamphetamine treatment induces circadian activity rhythms in arrhythmic animals with suprachiasmatic nucleus lesions or clock gene deletions. Activation of dopaminergic neurotransmission by methamphetamine is considered to induce activity rhythms. Adenosine antagonizes the actions of dopamine at heteromers of dopamine and adenosine receptors (dopamine D1 and adenosine A1 receptors, dopamine D2 and adenosine A2A receptors). In this study, we considered that adenosine inhibition acts similarly to methamphetamine, and administered an antagonist of adenosine A1 and A2A receptors, caffeine, in drinking water. Chronic caffeine treatment extended the circadian activity period of wild-type mice under constant darkness. The circadian period extension continued for three weeks after the replacement of caffeine with water. Chronic caffeine treatment induced circasemidian (~12 h), circadian, and longer-period activity rhythms in clock gene deficient, cryptochrome (Cry) 1 and Cry 2 double knockout mice under constant darkness. These activity rhythms changed periods spontaneously over time and became arrhythmic upon caffeine withdrawal. In humans, rhythms with shorter or longer than 24 h periods are hypothesized to cause internal desynchronization of the sleep-wake rhythm from the ~ 24 h body temperature rhythm under temporal isolation. Circasemidian rhythms are hypothesized to cause afternoon sleepiness and nap. Caffeine-induced rhythms may help in understanding rhythms with not around 24 h periods in humans.
14 Apr 2023Submitted to European Journal of Neuroscience
15 Apr 2023Submission Checks Completed
15 Apr 2023Assigned to Editor
17 Apr 2023Review(s) Completed, Editorial Evaluation Pending
17 Apr 2023Reviewer(s) Assigned
18 Aug 2023Editorial Decision: Revise Major
04 Nov 20231st Revision Received
06 Nov 2023Submission Checks Completed
06 Nov 2023Assigned to Editor
06 Nov 2023Review(s) Completed, Editorial Evaluation Pending
06 Nov 2023Reviewer(s) Assigned