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.
KEYWORDS
caffeine, adenosine receptors,
circasemidian rhythm, circadian rhythm, cryptochrome