Sleep and its homeostatic regulation in mice lacking the adenosine A1 receptor.
Sleep deprivation (SD) increases extracellular adenosine levels in the basal forebrain, and pharmacological manipulations that increase extracellular adenosine in the same area promote sleep. As pharmacological evidence indicates that the effect is mediated through adenosine A1 receptors (A1R), we expected A1R knockout (KO) mice to have reduced rebound sleep after SD. Male homozygous A1R KO mice, wild-type (WT) mice, and heterozygotes (HET) from a mixed 129/C57BL background were implanted during anesthesia with electrodes for electroencephalography (EEG) and electromyography (EMG). After 1 week of recovery, they were allowed to adapt to recording leads for 2 weeks. EEG and EMG were recorded continuously. All genotypes had a pronounced diurnal sleep/wake rhythm after 2 weeks of adaptation. We then analyzed 24 h of baseline recording, 6 h of SD starting at light onset, and 42 h of recovery recording. Neither rapid eye movement sleep (REM sleep) nor non-REM sleep (NREMS) amounts differed significantly between the groups. SD for 6 h induced a strong NREMS rebound in all three groups. NREMS time and accumulated EEG delta power were equal in WT, HET and KO. Systemic administration of the selective A1R antagonist 8-cyclopentyltheophylline (8-CPT) inhibited sleep for 30 min in WT, whereas saline and 8-CPT both inhibited sleep in KO. We conclude that constitutional lack of adenosine A1R does not prevent the homeostatic regulation of sleep.
Stenberg
Dag
D
Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland. dag.stenberg@helsinki.fi
Litonius
Erik
E
Halldner
Linda
L
Johansson
Björn
B
Fredholm
Bertil B
BB
Porkka-Heiskanen
Tarja
T
D000222:Adaptation, Physiological; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016548:Prosencephalon / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000378:metabolism / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism*; D012895:Sleep, REM / Q000502:physiology*
D043682:Receptor, Adenosine A1