Histaminergic System (histaminergic + system)

Distribution by Scientific Domains


Selected Abstracts


Histamine-1 receptor is not required as a downstream effector of orexin-2 receptor in maintenance of basal sleep/wake states

ACTA PHYSIOLOGICA, Issue 3 2010
M. Hondo
Abstract Aim:, The effect of orexin on wakefulness has been suggested to be largely mediated by activation of histaminergic neurones in the tuberomammillary nucleus (TMN) via orexin receptor-2 (OX2R). However, orexin receptors in other regions of the brain might also play important roles in maintenance of wakefulness. To dissect the role of the histaminergic system as a downstream mediator of the orexin system in the regulation of sleep/wake states without compensation by the orexin receptor-1 (OX1R) mediated pathways, we analysed the phenotype of Histamine-1 receptor (H1R) and OX1R double-deficient (H1R,/,;OX1R,/,) mice. These mice lack OX1R-mediated pathways in addition to deficiency of H1R, which is thought to be the most important system in downstream of OX2R. Methods:, We used H1R deficient (H1R,/,) mice, H1R,/,;OX1R,/, mice, OX1R and OX2R double-deficient (OX1R,/,;OX2R,/,) mice, and wild type controls. Rapid eye movement (REM) sleep, non-REM (NREM) sleep and awake states were determined by polygraphic electroencephalographic/electromyographic recording. Results:, No abnormality in sleep/wake states was observed in H1R,/, mice, consistent with previous studies. H1R,/,;OX1R,/, mice also showed a sleep/wake phenotype comparable to that of wild type mice, while OX1R,/,; OX2R,/, mice showed severe fragmentation of sleep/wake states. Conclusion:, Our observations showed that regulation of the sleep/wake states is completely achieved by OX2R-expressing neurones without involving H1R-mediated pathways. The maintenance of basal physiological sleep/wake states is fully achieved without both H1 and OX1 receptors. Downstream pathways of OX2R other than the histaminergic system might play an important role in the maintenance of sleep/wake states. [source]


Targeting of the central histaminergic system for treatment of obesity and associated metabolic disorders

DRUG DEVELOPMENT RESEARCH, Issue 8 2006
Kjell Malmlöf
Abstract There is currently a need for effective pharmacological therapies for treatment of obesity. In this communication, the involvement of the neurotransmitter histamine in the regulation of food intake is reviewed, together with results obtained in animals with pharmacologically increased brain histamine levels. A survey of the literature reveals that histaminergic circuits, arising from nerve cell bodies in the tuberomammillary nucleus and projecting into the paraventricular nucleus, the arcuate nucleus, and the ventromedial hypothalamus, are strongly involved in regulation of food intake and possibly also energy expenditure. Current literature also suggests the histaminergic circuits connect to other neuronal pathways involved in the regulation of energy balance and body weight. Studies performed in rodents demonstrate that H3 receptor antagonists increase hypothalamic histamine and decrease food intake, which result in decreased body weight. Lipid oxidation is increased and, at higher doses, body fat is also decreased. These changes are associated with lower circulating levels of insulin during an oral glucose challenge suggesting an increase in insulin sensitivity. The effects on food intake have also been confirmed in pigs and rhesus monkeys. It can thus be concluded that results obtained with H3 antagonist in animals warrant future clinical studies to evaluate whether this principle is effective in the treatment of human obesity. Drug Dev. Res. 67:651,665, 2006. © 2006 Wiley-Liss, Inc. [source]


Modulation of histamine H3 receptors in the brain of 6-hydroxydopamine-lesioned rats

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000
Oleg V. Anichtchik
Abstract Parkinson's disease is a major neurological disorder that primarily affects the nigral dopaminergic cells. Nigral histamine innervation is altered in human postmortem Parkinson's disease brains. However, it is not known if the altered innervation is a consequence of dopamine deficiency. The aim of the present study was to investigate possible changes in the H3 receptor system in a well-characterized model of Parkinson's disease , the 6-hydroxydopamine (6-OHDA) lesioned rats. Histamine immunohistochemistry showed a minor increase of the fibre density index but we did not find any robust increase of histaminergic innervation in the ipsilateral substantia nigra on the lesioned side. In situ hybridization showed equal histidine decarboxylase mRNA expression on both sides in the posterior hypothalamus. H3 receptors were labelled with N-alpha-[3H]-methyl histamine dihydrochloride ([3H] NAMH). Upregulation of binding to H3 receptors was found in the substantia nigra and ventral aspects of striatum on the ipsilateral side. An increase of GTP-,-[35S] binding after H3 agonist activation was found in the striatum and substantia nigra on the lesioned side. In situ hybridization of H3 receptor mRNA demonstrated region-specific mRNA expression and an increase of H3 receptor mRNA in ipsilateral striatum. Thus, the histaminergic system is involved in the pathological process after 6-OHDA lesion of the rat brain at least through H3 receptor. On the later stages of the neurotoxic damage, less H3 receptors became functionally active. Increased H3 receptor mRNA expression and binding may, for example, modulate GABAergic neuronal activity in dopamine-depleted striatum. [source]


Study on the antinociceptive action of Tyr-K-MIF-1, a peptide from the MIF family

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2007
R. Zamfirova
Summary 1 Tyr-K-MIF-1 is a melanocyte inhibiting factor (MIF) neuropeptide, isolated from the brain. Opposite to other MIFs (Tyr-MIF-1, Tyr-W-MIF-1), it has a very low affinity for opiate , -receptors, but interacts with Tyr-MIF-1 specific binding sites. Tyr-MIF-1 and Tyr-W-MIF-1 evoke antinociception mainly by activating opioid receptors. We investigated the possible antinociceptive effect of Tyr-K-MIF-1 and the involvement of histaminergic system in its mechanism of action. 2 Tested on rats by paw-pressure test, Tyr-K-MIF-1 (0.5, 1 and 2 mg kg,1) was associated with short-lasting analgesia, which was abolished by naloxone (1 mg kg,1). 3 Injected intraperitoneally (i.p.) 15 min before Tyr-K-MIF-1, antagonists of H1 (diphenhydramine, 100 mg kg,1) or H2 (famotidine, 0.3 and 0.6 mg kg,1) histamine receptors diminished peptide antinociceptive effect. Simultaneous H1 - and H2 blockade, as well as pretreatment with 5 mg kg,1 dimaprit (H2 agonist) abolished Tyr-K-MIF-1-induced analgesia. Tyr-K-MIF-1-induced analgesia was also abolished by treatment with R-(,)-methylhistamine (10 mg kg,1, i.p.), an H3 histamine receptor agonist that acts to inhibit histamine release. 4 Our results together with data reported in the literature support the conclusion that activation of the histaminergic system is involved in the mechanism of Tyr-K-MIF-1-induced antinociception. [source]


Intracerebroventricular Effects of Histaminergic Agents on Morphine-Induced Anxiolysis in the Elevated Plus-Maze in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2005
Mohammad-Reza Zarrindast
It has also been reported that histaminergic system can interfere with some pharmacological effects of morphine. The effects of histaminergic agents on morphine-induced anxiolysis in rats, using elevated plus-maze were investigated in the present study. Intraperitoneal injection of morphine (3, 6 and 9 mg/kg) induced antianxiety effects. Intracerebroventricular administration of histamine at the doses of (5, 10 and 20 ,g/rat) also increased anxiety-related behaviours. Intracerebroventricular injection of pyrilamine, a H1 receptor antagonist (25, 50 and 100 ,g/rat), increased anxiety whereas injection of ranitidine, a H2 receptor antagonist (5, 10 and 20 ,g/rat) at the same site, decreased anxiety. Therefore, it seems that histamine induces anxiogenic response through activation of H2 receptors, while the response of H1 blocker may be due to release of histamine. We also evaluated the interactions between morphine and histaminergic agents. Our data show that histamine (10 ,g/rat), pyrilamine (50 ,g/rat) and ranitidine (5 ,g/rat) did not alter the response induced by different doses of morphine (3, 6 and 9 mg/kg). Similarly, a single dose of morphine did not alter the response induced by different doses of histamine (5, 10 and 20 ,g/rat), pyrilamine (25, 50 and 100 ,g/rat) or ranitidine (5, 10 and 20 ,g/rat). In conclusion, the histaminergic system plays an important role in the modulation of anxiety, although in our experiments, no interaction was found between the effects of histaminergic agents and morphine on anxiety-related indices in the elevated plus-maze. This may imply that morphine-induced anxiolysis probably is independent of the histaminergic system. [source]