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The present study examined the expression pattern of FOS in the hypothalamic peptide neurons during the sleep-dominant state induced by an adenosine A2A receptor agonist. The control rats, those that received the microdialysis-perfusion of their ventral striatum with artificial cerebrospinal fluid in the dark-active phase, spent 24% of the 90-min period prior to sacrifice in non-rapid eye movement (non-REM) sleep and 2.3% of that in REM sleep. These rats exhibited FOS, a transcription factor, in 21% of their orexin neurons and in 1.0% of their melanin-concentrating hormone (MCH) neurons in the perifornical/lateral hypothalamic areas. However, the rats perfused with 50 microM CGS21680, an adenosine A2A receptor agonist, spent 60% of the 90-min period prior to sacrifice in non-REM sleep and 11% of that in REM sleep. These rats exhibited FOS in 1.7% of their orexin neurons and FOS in 0.5% of their MCH neurons. When the sleep-dominant state was disturbed by mild stimulation and the rats were kept in the sleepy state by treatment with a sleep-inducing dose of CGS21680, the rats exhibited FOS in 13.3% of their orexin neurons, which percentage was about half of that for the control rats. These results suggest that the sleep-promoting process induced by this adenosine A2A receptor agonist was associated with a decline in the activity of orexin neurons. MCH neurons are not likely to change their activities during this sleep-promoting process.

The level of hypocretin-1 (orexin A) is reported to be low in the cerebrospinal fluid (CSF) of subjects with narcolepsy. We measured the CSF level of hypocretin-1 of two young hypersomniacs. The first subject was a 9-year-old boy who exhibited cataplexy, and was demonstrated to be human leukocyte antigen-DR2 (HLA-DR2) positive. The second subject was a 16-year-old boy who exhibited no cataplexy and was HLA-DR2 negative. When excessive daytime sleepiness ensued, appetite and bodyweight were increased in case 1 but not in case 2. The level of CSF hypocretin-1 was undetectably low and within normal limits in case 1 and case 2, respectively. It appears to be important to measure the CSF level of hypocretin-1 in the diagnosis and treatment of narcolepsy.