Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: an in vivo microdialysis study
Section snippets
Experimental animals and surgery
Adult male cats were housed under constant temperature, with ad libitum access to food and water. Under pentobarbital anesthesia, animals were surgically implanted with electrodes for recording electroencephalogram, electrooculogram, electromyogram and ponto-geniculate-occipital waves for determination of behavioral state. In each subject, four to six intracerebral guide cannulae (CMA 10 guide, CMA/Microdialysis, Stockholm, Sweden) were implanted above the target sites for later insertion of
Control experiments
Immediately after the probe insertion the extracellular adenosine concentrations were high, but declined spontaneously to the basal level within 6 h; mean concentration in sample was 32.8±3.0 nmol/l (mean±S.E.M., n=10 probes in the BF and the thalamus) (Fig. 1A). Adenosine concentrations were also measured on four consecutive days from two samples collected each day during wakefulness (n=10 probes in the BF). There was no significant difference in the basal adenosine concentrations between the
Adenosine levels during sleep deprivation and recovery sleep
The present study has extended our description of the state-related changes in extracellular adenosine levels measured previously only in the BF and thalamus to four additional brain areas in order to determine if the earlier findings were site-specific.29 Perhaps the most important present finding is that, during prolonged wakefulness, extracellular adenosine accumulated in a site-specific manner. In the BF (n=8) adenosine levels rose steadily and monotonically during each of the 6 h of sleep
Conclusions
During natural sleep–wake cycles the changes in extracellular adenosine concentrations were similar in all brain areas studied: wakefulness>non-REM=REM sleep. During 6 h of sleep deprivation, adenosine levels increased significantly in the BF and, to a lesser extent in the cortex, but not in any other subcortical structures tested to date. This site-specific accumulation of adenosine during sleep deprivation indicates the existence of physiological regulation of adenosine levels, by as yet
Acknowledgements
This work was supported by the National Institute of Mental Health (NIMH 39683) and the Department of Veterans Affairs Medical Research Service Awards to RES and RWM. We thank Dr Dag Stenberg and Dr Mahesh Thakkar for helpful consultations in the course of the work, Drs Carl Olson and P. Shiromani for anatomical consultation, Lynda Dauphin for histological work and running the experiments with us, and Kara Rebello, Russell Delgiacco, and Rachel Aronson for technical assistance.
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These authors contributed equally to this work.