The dose-response effects of caffeine on sleep in rats

Caffeine at doses of 0.125, 1.25, 12.5 and 25 mg/kg was administered to rats and the subsequent effects on the sleep-wake cycle were measured. The 12.5 and 25 mg/kg doses of caffeine increased wakefulness, and decreased slow wave sleep-1 (SWS1), SWS2, rapid eye movement (REM) sleep and total sleep time (P less than or equal to 0.05). The 0.125 and 1.25 mg/kg doses of caffeine increased SWS1 at the expense of SWS2 (P less than or equal to 0.05), and did not affect total sleep time in any time period measured. Adenosine or adenosine agonists have been shown to increase SWS2 at the expense of waking or SWS1 with an increase in total sleep time. The effects of caffeine on sleep reported in this study suggest that caffeine administration not only antagonizes the effects of adenosine at the receptor level, but also at the behavioral level.

[1]  J. Phillis,et al.  Behavioral interaction of adenosine and methylxanthines on central purinergic systems , 1984, Neuroscience Letters.

[2]  Robert L. Williams,et al.  Dose‐related sleep disturbances induced by coffee and caffeine , 1976, Clinical pharmacology and therapeutics.

[3]  G. Di Chiara,et al.  Sleep induced by low doses of apomorphine in rats. , 1979, Electroencephalography and clinical neurophysiology.

[4]  S. Snyder,et al.  Behavioral and molecular actions of caffeine: focus on adenosine. , 1984 .

[5]  V. Březinová,et al.  Effect of caffeine on sleep: EEG study in late middle age people. , 1974, British journal of clinical pharmacology.

[6]  M. Radulovački,et al.  Adenosine analogs and sleep in rats. , 1984, The Journal of pharmacology and experimental therapeutics.

[7]  Phillis Jw,et al.  Adenosine, adenylate cyclase, and transmitter release. , 1985 .

[8]  J. Daly Adenosine receptors: targets for future drugs. , 1982, Journal of medicinal chemistry.

[9]  S H Snyder,et al.  Adenosine receptors and behavioral actions of methylxanthines. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Miodrag Radulovacki,et al.  Caffeine produces REM sleep rebound in rats , 1980, Brain Research.

[11]  A Sattin,et al.  The effect of adenosine and adenine nucleotides on the cyclic adenosine 3', 5'-phosphate content of guinea pig cerebral cortex slices. , 1970, Molecular pharmacology.

[12]  R. S. Miletich,et al.  N6 (L-Phenylisopropyl)adenosine (L-PIA) increases slow-wave sleep (S2) and decreases wakefulness in rats , 1982, Brain Research.