Wake-promoting neuronal

Most hypnotic drugs act on GABA receptors. It is reasonable to hypothesize that hypnotic actions are mediated by the GABA receptors on wake-promoting neurons innervated by POA sleep-active neurons, but there is little study of this problem. However, there is evidence that GABAergic anesthetics induce c-Fos IR in the VLPO and suppress c-Fos IR in histaminergic neurons (Nelson et al, 2002). 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

Grivel, J., Cvetkovic, V., Bayer, L. el al. (2005). The wake-promoting hypocretin/orexin neurons change their response to noradrenaline after sleep deprivation. J. Neurosci 25, 4127-30. 

IL-ip and TNF-a promote NREM sleep through multiple brain sites. IL-1 excites sleep-active neurons and inhibits wake-active neurons in the AH/MPO (50). Some hypothalamic neurons are receptive for both IL-ip and GHRH and these neurons are GABAergic (27). IL-ip upregulates hypothalamic GHRH receptors and may also stimulate GHRH synthesis (51). IL-ip injected into the locus ceruleus (52) and dorsal raphe (53) also enhances sleep. Promotion of NREM sleep occurs after microinjection of TNF-a into the AH/MPO (54) or the locus ceruleus (52). 

Gallopin T, Luppi PH, Rambert FA, Frydman A, Fort P (2004) Effect of the wake-promoting agent modafinil on sleep-promoting neurons from the ventrolateral preoptic nucleus an in vitro pharmacologic study. Sleep 27 19-25... 

During the last decade, research lent support to the idea that three interacting neuronal systems (a wake-promoting system, a NREM-promoting system and a REM-... 

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