Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep

摘要: Adenosine has been proposed to promote sleep through A(1) receptors (A(1)R's) and/or A(2A) in the brain. We previously reported that mediate sleep-promoting effect of prostaglandin D(2), an endogenous sleep-inducing substance, and activation these induces blockade them by caffeine results wakefulness. On other hand, A(1)R suggested increase inhibition cholinergic region basal forebrain. However, role target sites sleep-wake regulation remained controversial. In this study, immunohistochemistry revealed was expressed histaminergic neurons rat tuberomammillary nucleus (TMN). vivo microdialysis showed histamine release frontal cortex decreased microinjection into TMN N(6)-cyclopentyladenosine (CPA), agonist, adenosine or coformycin, inhibitor deaminase, which catabolizes inosine. Bilateral injection CPA significantly increased amount delta power density non-rapid eye movement (non-REM; NREM) but did not affect REM sleep. CPA-promoted observed WT mice KO for H(1) receptor, indicating NREM promoted A(1)R-specific agonist depended on system. Furthermore, bilateral coformycin sleep, completely abolished coadministration 1,3-dimethyl-8-cyclopenthylxanthine, a selective antagonist. These indicate suppresses system via