Hypothalamus histamine effects

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Although histamine has mixed excitatory and inhibitory effects on central neurons, those antihistamines (Hi-receptor antagonists) that enter the brain produce sedation this indicates that the predominant overall effect of histamine is excitatory. The preferred explanation for this rests on evidence that histaminergic neurons in the posterior hypothalamus are active in waking and silent in deep SWS and REM sleep. 

Figure 6.3 Histamine release measured from the posterior hypothalamus of freely behaving cats across the sleep-wakefulness cycle. The histamine release was higher during wakefulness compared with non-REM and REM sleep in each experiment, producing a highly significant group effect. Each experiment is represented by a single line (n = 5). Adapted from Strecker et al. (2002), to which the reader is referred for more details.

Ishizuka, T., Yamamoto, Y. Yamatodani, A. (2002). The effect of orexin-A and -B on the histamine release in the anterior hypothalamus in rats. Neurosci. Lett. 323, 93-6. 

Some CNS stimulants have an effect on the same systems that are involved in wakefulness, including glutamate-, NE-, DA-, 5-HT-, histamine-, hypocretin- and ACh-containing neurons. This group includes molecules such as cocaine, amphetamine, and nicotine. The sleep-promoting systems are concentrated in the medial part of the brainstem, dorsal reticular substance of the medulla, anterior hypothalamus, and basal forebrain (Jones 2005). Other stimulants, such as caffeine and theophylline, block some sleep-inducing mechanisms. Modafinil is also a CNS stimulant with an unknown mechanism of action. 

Dopamine has an alerting effect. Neurochemicals involved in wakefulness include norepinephrine and acetylcholine in the cortex and histamine and neuropeptides (e.g., substance P and corticotropin-releasing factor) in the hypothalamus. 

The neurotransmitter histamine (HA) exerts several functions in the hypothalamus [1-2] including an involvement in the neuroendocrine regulation of pituitary hormone secretion [3]. HA has no effect directly at the level of the pituitary gland, but influences the secretion of anterior pituitary hormones either by an exerted e.g. in the paraventricular nucleus (PVN) on other central transmitters or hypothalamic regulating factors, which subsequently regulate the release of anterior pituitary hormones. In addition, HA acts on the supraoptic nucleus (SON) in the hypothalamus where the posterior pituitary hormones are synthesized and thereby exerts a direct effect on the release of the posterior pituitary hormones. Immunohistochemical studies have revealed that the histaminergic neurons, which originate in the tuberomammillary nuclei of the posterior hypothalamus, densely innervate most of the hypothalamic areas involved in the neuroendocrine control of pituitary hormone secretion [4-5]. Within the last two decades the effect of HA on pituitary hormone secretion have been explored in several studies and it has been... 

The modulation of the N-type Ca2+ channels has been shown for some presynaptic receptors to be the mechanistic basis for the inhibition of Ca2+ influx [29]. In 1989 Takemura et al. [30] reported on the effective inhibition of histamine release from rat hypothalamic slices by the N-type Ca2+ -channel blocker ca-conotoxin. In addition Endou et al. [23] showed that to-conotoxin greatly potentiated the modulatory effect of (R)a-methylhistamine on cardiac adrenergic responses. Yang and Hatton [31] provided direct evidence for an H3 receptor-mediated modulation of ion permeability of neurons. They showed that in magnocellular histaminergic neurons from the rat posterior hypothalamus, H3... 

Figure 3 Effect of thioperamide on histamine release measured by in vivo microdialysis in the anterior hypothalamus. P< 0.05 us. control group. The basal output is defined as an average of the first 3 fractions before injection of saline or thioperamide, and subsequent fractions Eire expressed as percentages of it (mean S.E.). Data from Mochizuki et al. (1991) (19).

Studies in brain slices have shown that histamine is one of the most powerful agents in stimulating cyclic AMP accumulation in the mammalian central nervous system [ 146]. Early studies in the rabbit showed that histamine elicited very large increases in the accumulation of cyclic AMP in cerebral cortex (12-16-fold increase above basal levels), hypothalamus (20-30-fold), brain stem (35-fold) and cerebellum (3-10-fold) [155, 156]. The effect in cerebral cortex has subsequently been studied by a number of other groups and increases in cyclic AMP accumulation as high as 74-fold above basal levels have been reported [82, 157, 158]. Furthermore, the response to histamine in rabbit cerebral cortical slices appears to depend on the age of the animal and increases markedly during the first 8 days postpartum before declining to adult levels [157],... 

Histamine-stimulated adenylate cyclase activity is observed in only three of the regions so far examined in guinea-pig brain, namely hippocampus, cerebral cortex and striatum, and no effect has been observed in cerebellum, hypothalamus, thalamus, midbrain and pons-medulla [179]. Interestingly, this is exactly the distribution of H2-receptors deduced from binding studies with [3H]tiotidine [133]. 

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