Feeding-induced increase in the extracellular concentration of histamine in rat hypothalamus as measured by in vivo microdialysis

Department of Pharmacology, Okayama University, Okayama, Okayama, Japan
Neuroscience Letters (Impact Factor: 2.03). 05/1991; 125(2):235-237. DOI: 10.1016/0304-3940(91)90037-T


The extracellular concentration of histamine (HA) in the hypothalamus of conscious and freely moving rats was measured by in vivo microdialysis and the effects of fasting and feeding on the HA concentration were examined. In non-fasted rats, the basal HA concentration was almost constant from 11.00 to 17.00 h on the day following implantation of the dialysis probe, the mean value being . No significant change in the HA concentration was observed in rats deprived of food for 24 h. In 24-h fasted rats, feeding for 15 min produced a transient and significant increase in the HA concentration. These results suggest that histaminergic activity in the rat hypothalamus increases during feeding.

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    • "By contrast, increasing the availability of endogenous histamine suppresses appetite (Sheiner et al., 1985; Ookuma et al., 1993; Malmlof et al., 2007; Ishizuka et al., 2008). The level of histamine in the hypothalamus increases with appetitive behaviour (Itoh et al., 1991), and the mediobasal region of the hypothalamus has been proposed as a site of action following region-specific injections of histaminergic drugs (Sakata et al., 1988; 1990; Fukagawa et al., 1989). Specifically, the ventromedial nucleus (VMN) of the hypothalamus has long been known as an important 'satiety' centre from classic brain-lesioning studies, and to be the region most densely populated with glucose-sensing neurones (King, 2006). "
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    ABSTRACT: BACKGROUND AND PURPOSE Centrally acting histamine H(3) receptor ligands are proposed as potential treatments for obesity, although the value of inverse agonists at these receptors is still debated. Functional inhibition of H(3) autoreceptors activates neurones in a hypothalamic 'satiety' centre. The H(3) receptor antagonist, proxyfan was used as a tool to assess the action of histaminergic compounds in this model. EXPERIMENTAL APPROACH We compared the actions of histamine on feeding with those of an H(3) receptor agonist (imetit) and inverse agonist (thioperamide) in rats and mice. Sites of action were identified by immunohistochemistry and the hypothalamic ventromedial nucleus (VMN) was investigated using electrophysiological techniques. KEY RESULTS Central histamine or thioperamide decreased fast-induced feeding, whereas imetit increased feeding. Systemic thioperamide entered the brain to activate hypothalamic feeding centres and to reduce feeding without causing any adverse behaviours. Thioperamide activated neurones in the VMN through an action on histamine autoreceptors, whilst imetit had the opposite effect. Proxyfan administered alone did not affect either feeding or electrical activity. However, it blocked the actions of both thioperamide and imetit, acting as a neutral antagonist in this system. CONCLUSIONS AND IMPLICATIONS The H(3) receptor inverse agonist, thioperamide, potently reduced appetite without adverse behavioural effects. This action was blocked by proxyfan, acting as a neutral antagonist in this model and, therefore, this compound is useful in determining the selectivity of H(3) receptor-directed drugs. A major action of thioperamide is through presynaptic autoreceptors, inducing stimulation by endogenous histamine of postsynaptic H(1 ) receptors on anorectic hypothalamic neurones.
    British Journal of Pharmacology 05/2012; 167(5):1099-110. DOI:10.1111/j.1476-5381.2012.02056.x · 4.84 Impact Factor
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    • "In this study using a brain microdialysis technique to measure extracellular histamine levels in the anterior hypothalamus, it was demonstrated that a transient and significant increase in histamine concentration was produced when rats were fed for 1 h, while no significant change in histamine release was observed in the non-fed group, which was similarly trained but was not given chow on the day of microdialysis (Figure 1). Another research group also showed similar results when they observed hypothalamic histamine release during feeding in 24 h-fasted rats (Itoh et al., 1991). Vald├ęs et al. (2010) showed histamine release in the posterior hypothalamic area when hungry rats were trying "
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    ABSTRACT: Feeding behavior is regulated by a complex interplay of many endogenous substances, such as peptides and neurotransmitters in the central nervous system. Histamine is a neurotransmitter which expresses an anorectic effect on food intake via histamine H(1) receptors. The histaminergic system exists downstream of leptin, a satiety factor secreted from white adipose tissue. Because direct stimulation of the histaminergic system by histamine H(3)-inverse agonists or antagonists can normalize the obese phenotype in which animal models with exogenous leptin resistance, which resembles human obesity, the potential roles of histamine H(3) receptors as a therapeutic target now draw attention. Histaminergic activity is enhanced during feeding, and an oral somatic sensation is thought to affect histaminergic activity while blood glucose levels do not. In addition, gustatory information can modulate histaminergic activity by two mechanisms: by physiological excitation of the chorda tympani nerve, one of the taste nerves and by emotions elicited by taste perception, i.e., taste palatability. Particularly, aversive and hazardous taste stimuli tonically facilitate histaminergic activity, suggesting that the histaminergic system is involved in the response to harmful stimuli. Together with recent findings, it is postulated that the histaminergic system responds to both mechanical and chemical sensory input from the oral cavity during feeding and is exerted as a part of the danger response system.
    Frontiers in Systems Neuroscience 05/2012; 6:44. DOI:10.3389/fnsys.2012.00044
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    • "Hypothalamic levels of the endocannabinoid 2-arachydonoylethanolamide increase during fasting and are lowest during food consumption (Kirkham et al., 2002); on the other hand, histaminergic cells activity increases during food presentation to fasted rats (Meynard et al., 2005) and remains sustained during feeding (Itoh et al., 1991). However, nothing is known about the temporal and causal relationship between the histaminergic and cannabinoid systems in controlling appetitive behaviour, an issue that deserves further investigation. "
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    ABSTRACT: Cannabinoids exert complex actions on neurotransmitter systems involved in cognition, locomotion, appetite, but no information was available so far on the interactions between the endocannabinoid system and histaminergic neurons that command several, similar behavioural states and memory. In this study, we investigated the effect of cannabimimetic compounds on histamine release using the microdialysis technique in the brain of freely moving rats. We found that systemic administration of the cannabinoid receptors 1 (CB1-r) agonist arachidonyl-2'chloroethylamide/N-(2chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA; 3 mg/kg) increased histamine release from the posterior hypothalamus, where the histaminergic tuberomamillary nuclei (TMN) are located. Local infusions of ACEA (150 nm) or R(+)-methanandamide (mAEA; 1 microm), another CB1-r agonist, in the TMN augmented histamine release from the TMN, as well as from two histaminergic projection areas, the nucleus basalis magnocellularis and the dorsal striatum. When the endocannabinoid uptake inhibitor AM404 was infused into the TMN, however, increased histamine release was observed only in the TMN. The cannabinoid-induced effects on histamine release were blocked by co-administrations with the CB1-r antagonist AM251. Using double-immunofluorescence labelling and confocal laser-scanning microscopy, CB1-r immunostaining was found in the hypothalamus, but was not localized onto histaminergic cells. The modulatory effect of cannabimimetic compounds on histamine release apparently did not involve inhibition of gamma-aminobutyric acid (GABA)ergic neurotransmission, which provides the main inhibitory input to the histaminergic neurons in the hypothalamus, as local infusions of ACEA did not modify GABA release from the TMN. These profound effects of cannabinoids on histaminergic neurotransmission may partially underlie some of the behavioural changes observed following exposure to cannabinoid-based drugs.
    European Journal of Neuroscience 10/2006; 24(6):1633-44. DOI:10.1111/j.1460-9568.2006.05046.x · 3.18 Impact Factor
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