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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.

Prostaglandin (PG) E 2 reportedly augmented wakefulness when continuously infused into the third ventricle of the rat brain, whereas it promoted sleep when continuously infused into the subarachnoid space of the ventral surface zone of the rostral basal forebrain, which was designated previously as a PGD 2 -sensitive sleep-promoting zone (PGD 2 -SZ). In the present study, we investigated the effects of PGE (EP)-receptor agonists on sleep-wakefulness activities by infusing agonists into the third ventricle or into the subarachnoid space of the PGD 2 -SZ. Our results indicated that the waking effect is mediated by EP 1 and EP 2 receptors situating around the third ventricle, whereas the sleep-promoting effect is brought about mainly through activation of EP4 receptors located at or near the subarachnoid space of the PGD 2 -SZ.

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.