Histamine arousal

From time to time it has been suggested that histamine has some role in a number of behaviours and motor activity while the established and marked sedative effect of Hi receptor antagonists, mentioned at the start of this section, has consistently been considered to indicate a role for histamine in arousal and the sleep-waking cycle (see Chapter 22). 

Histamine release in the hypothalamus is higher during the active waking than the quiescent phase of behaviour, whether this is associated with darkness (in rats) or light (rhesus monkey). The firing rate of histamine neurons is also higher during arousal... 

It is important to emphasise that a lesion of the reticular system disrupts a number of afferent inputs to the cortex. Particularly important in this respect are the mono-aminergic (especially noradrenaline, 5-HT and histamine) and cholinergic pathways. When the ascending inputs from these neurons are destroyed, sleep is passive and not at all like natural sleep which, as detailed above, has distinct phases and depends on brainstem influences on cortical function. How these different neurotransmitters might influence sleep and arousal will be considered next. 

Figure 22.7 Histamine influences on sleep and arousal. The activity of histamine-releasing neurons increases with arousal and diminishes during sleep. Both Hi antagonists and agonists of H3-autoreceptors depress release of histamine and reduce arousal (see text for details)...

Brown, R. E., Sergeeva, O. A., Eriksson, K. S. Haas, H. L. (2002). Convergent excitation of dorsal raphe serotonin neurons by multiple arousal systems (orexin/hypocretin, histamine and noradrenaline). J. Neurosci. 22, 8850-9. 

Kalivas, P. W. (1982). Histamine-induced arousal in the conscious and pentobarbital-pretreated rat. J. Pharmacol Exp. Then 222, 37-42. 

McCormick, D. A. Williamson, A. (1991). Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine possible cellular mechanisms of histaminergic control of arousal. J. Neurosci 11, 3188-99. 

Histamine in the nervous system may participate in a variety of brain functions. Several of the suspected physiological roles for histamine are related to its ability to increase the neuronal excitability [1, 2,15]. For example, mutant mice lacking the H, receptor show defective locomotor and exploratory behaviors [57], Neuronal histamine may increase attention and/or arousal by many mechanisms, including by enhancing sensory input [58], All available evidence from several species shows that histaminergic neurons, when activated, increase wakefulness... 

Drugs that act on the H3 receptor are being developed for the treatment of obesity, sleep disturbances, epilepsy and cognitive disorders. The ability of histamine to promote arousal, suppress appetite, elevate seizure threshold and stimulate cognitive processes implies that compounds able to enhance the release of neuronal histamine should mimic these effects. Several H3 antagonists currently in development demonstrate such activity and show promise as effective and novel therapeutic agents [40, 84-86]. Because H3 agonists suppress the release of... 

HI receptors occur throughout the CNS with particularly high densities in the thalamus and hippocampus and are thought to mediate arousal effects of histamine. H2 receptors are concentrated in the striatum, hippocampus and thalamus and H3 receptors in cortex, hippocampus and amygdala. Histamine levels diminish during sleep and HI antagonists which cross the blood brain... 

Ascending histamine containing fibres originating from the reticular formation are considered important in arousal. Histaminergic neurons cease firing with the onset of sleep. Histamine antagonists (for the treatment of allergies) are... 

Non-mast cell histamine is found in several tissues, including the brain, where it functions as a neurotransmitter. Strong evidence implicates endogenous neurotransmitter histamine in many brain functions such as neuroendocrine control, cardiovascular regulation, thermal and body weight regulation, and sleep and arousal (see Chapters 21 and 37). 

But the fact that we experience anxiety—often of panic proportions in our REM sleep dreams when the locus coeruleus is shut down completely—means two things that arousal—at least in the waking sense of the term—and anxiety are completely dissociable and that the brain-mind is capable of generating anxiety without the help of the locus coeruleus In fact, REM sleep dream anxiety cannot depend upon norepinephrine, or serotonin, or histamine either, which leaves dopamine and acetylcholine as the only two neuromodulatory candidates for... 

The exact neurotransmitter role of histamine in the CNS remains an enigma. However, regulation of arousal and appetite by histamine has long been suggested by... 

HISTAMINE AND OREXIN One such neurotransmitter is histamine, whose neurons influence our level of arousal throughout the day. Lying next to these neurons is another group of neurons that release orexin, which is a neurotransmitter that influences both our level of arousal and craving for food. Take a moment to appreciate how the anatomical organization of this system optimizes your daily... 

Blockade of histamine autoreceptors increases histamine synthesis and release and may support higher CNS functions such as arousal, cognition and learning. Peripheral histamine heteroreceptors on C liber and on postganglionic sympathetic fiber terminals diminish neuropeptide and noradrenaline release, respectively. Both inhibititory effects are beneficial in myocardial ischemia. The inhibition of neuropeptide release also explains the antimigraine effects of some agonists of presynaptic histamine receptors. 

There is evidence that the histaminergic tract that passes from the posterior hypothalamus to the cortex via the thalamus is inhibited by a GABAergic pathway. It is now known that H3 receptors act as autoreceptors on histaminergic neurons and that agonists of H3 receptors augment slow-wave sleep. In addition, histamine can increase cortical arousal by enhancing excitatory cholinergic neurons from the basal forebrain and also inhibits the hypothalamic pre-optic area which normally promotes sleep. With respect to the control of the circadian rhythm, histamine has... 

Histamine is both a local hormone and a neurotransmitter in the central nervous system. It is synthesized in neurons and mast cells. There are Hi, H2, and H3 receptors in the central nervous system, but they differ in their localization, biochemical machinery, functions, and affinities for histamine they are particularly important in maintaining a state of arousal or awareness (1). 

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