somnogenic substance that progressively

accumulates with prolonged wakefulness, with adenosine being one of the most cited candidates.7 Both homeostatic and circadian mechanisms are thought, to influence the opposite action of neurons promoting wakefulness and neurons promoting sleep. Wake-active neurons are cholinergic (located in the basal forebrain and in the tegmentum) and monoaminergic (noradrenergic in the locus ceruleus, serotonergic in the dorsal raphe, and histaminergic in the tuberomammillary nucleus), whereas sleep-active neurons are GABAergic and located in the preoptic area of the hypothalamus:4 The discovery Inhibitors,research,lifescience,medical of the hypocretin (also called orexin) system has brought, new inroads into understanding Inhibitors,research,lifescience,medical the sleep-regulatory neural circuit.8 Hypocretin neurons are located in the lateral hypothalamus and have dense excitatory projections to all monoaminergic and cholinergic cell groups. Recent studies suggested that monoaminergic

and hypocretin neurons play a different and complementary role in wakefulness maintenance.4 For example, the dual effects of hypocretins on arousal and food intake (orexin from “appetite-stimulating”) suggest, a more important role for hypocretins in Inhibitors,research,lifescience,medical the control of arousal maintenance related to energy homeostasis.8 In the same way, data summarized in the following section suggest, a role for the norepinephrine (NE)-containing neurons of the locus ceruleus (LC) in stress-induced arousal and concomitant anxiety.

Interactions between stress, anxiety, and sleep Anxiety and stress Anxiety is a universal emotion and it, would at. times be maladaptive not. to experience it; it is a necessary part of the response of the organism to a stress, ie, a threat, to the psychological or the physiological integrity Inhibitors,research,lifescience,medical of an individual. Inhibitors,research,lifescience,medical Anxiety may be polarized between a state and a trait. It may supervene at. some point, in the course of life, in which case anxiety is referred as a state. Anxiety trait. is a long-term feature of a person’s experience, present. throughout, life and considered to be a key feature of the avoidant or anxious personality disorder. It. probably reflects a lifetime maladaptive response to stress due to individual differences in biogenetic background, Ku-0059436 cell line developmental influences, and early life experiences. There is no hard and fast, distinction between anxiety that may be considered as a normal, acceptable accompaniment of stress and the pathological state that warrants classification as a psychiatric secondly disorder. In the latter, the nature of the stress is not. always clearly discernible. In other words, pathological anxiety could be characterized by a sense of fear, but. it. is differentiated from fear in that the threat is not immediate or always obvious. Whether normal or pathological, the constituent, features of anxiety always comprise indices of increased arousal or alertness that, could lead to sleep-wake alterations.