Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors

Dai, Hongmei; Kaneko, Kenya; Katô, Hiroshi; Fujii, Satoshi; Jing, Yu‐Hong; Xu, Ajing; Sakurai, Eiko; Kato, Motohisa; Okamura, Nobuyuki; Kuramasu, Atsuo; Yanai, Kazuhiko

doi:10.1016/j.neures.2006.10.020

Cited by 116 publications

(104 citation statements)

References 45 publications

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“…In addition, we found that a long-term deficiency of histamine in HDC-KO mice accelerated the acquisition of contextual and cued fear responses, which suggests that an inhibitor of histaminergic neuronal activity may enhance fear memory. Notably, the cued fear response is enhanced in both histamine H1 and H2 receptor knockout mice [27] . Moreover, HDC-KO mice have improved contextual and cued fear responses, which are reversed by intracerebroventricular injection of histamine immediately after training [21] .…”

Section: Discussionmentioning

confidence: 99%

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

et al. 2010

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Aim: Histamine plays an important role in morphine addiction and memory-dependent behavior. However, little is known about the effect of histamine on the impairment of memory after morphine withdrawal. This study was designed to investigate the effect of histamine on memory impairment induced by morphine withdrawal in histidine decarboxylase knockout (HDC-KO) and wild-type (WT) mice. Methods: WT and HDC-KO mice were given subcutaneous morphine or saline twice daily for 5 consecutive days. The mice received a cued or contextual fear conditioning session 7 days after the last injection. During subsequent days, mice received 4 cued or contextual extinction sessions (one session per day). Western blot was used to assess extracellular signal-regulated kinase (ERK) phosphorylation in the amygdala and hippocampus. Results: Morphine withdrawal did not affect the acquisition of cued or contextual fear responses. It impaired cued but not contextual fear extinction. The acquisition of cued and contextual fear responses was accelerated in HDC-KO mice. Histamine deficiency aggravated the impairment of cued fear extinction induced by morphine withdrawal, whereas histamine (icv, 5 µg/mouse) reversed this effect. Morphine withdrawal decreased ERK phosphorylation in the amygdala after cued fear extinction, especially in HDC-KO mice. Conclusion: These results suggest that morphine withdrawal specifically impairs cued fear extinction and histamine ameliorates this impairment. Its action might be mediated by the modulation of ERK phosphorylation in the amygdala. Histamine should be explored for possible roles in the prevention or treatment of morphine abuse and relapse.

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Section: Discussionmentioning

confidence: 99%

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

et al. 2010

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“…Histamine mediates attention and vigilance upon stimulation of postsynaptic H 1 Rs and H 2 Rs in CNS. 237) H 3 R antagonists subsequently increase levels of histamine in distinct brain regions. Histaminergic neurotransmission in the TMN leads to activation of secondary pathways projecting into different brain areas associated with cognitive functions.…”

Section: )mentioning

confidence: 97%

Histamine H3 Receptor Antagonists Go to Clinics

Sander

Kottke

Stark

2008

Biological & Pharmaceutical Bulletin

185

118

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INTRODUCTIONThe biogenic amine histamine, 2-(1H-imidazol-4-yl)-ethanamine, is produced by decarboxylation of L-histidine and is implicated in a wide range of physiological and pathophysiological functions. It is metabolised by histamine N tmethyltransferase (HMT) and mono-or diaminoxidase. Histamine is mainly acting via four distinct metabotropic histamine receptor subtypes (H 1 R-H 4 R), which have meanwhile all been cloned. Whereas antagonists for H 1 R and H 2 R subtypes have been blockbusters in therapy of allergy and ulcer, respectively, antagonists for H 3 R and H 4 R subtypes are not on the market. The recently described H 4 R seems to be involved in inflammatory and immunomodulatory processes. H 3 Rs play a central role in neurotransmission of histamine and in control of many other neurotransmitters. Several antagonists are in preclinical and some in clinical stage of development. PHARMACOLOGICAL BACKGROUND Auto-and HeteroreceptorThe H 3 R was first described in 1983 as a presynaptic autoreceptor, which mediates synthesis of histamine and inhibition of its release from histaminergic neurons in slices of rat cerebral cortex. 1) Localisation studies in rodents show a predominance in distinct regions of the central nervous system (CNS) as the H 3 R is mainly located in cerebral cortex, hippocampus, amygdala, nucleus accumbens, globus pallidus, striatum, and hypothalamus 2-5) ( Fig. 1). In addition, it is expressed in the peripheral nervous system, e.g. in gastrointestinal tract, airways and cardiovascular system. 6) Molecular aspects of the receptor, [7][8][9][10] structure-activity relationships (SAR) of ligands, [11][12][13][14][15][16][17][18][19] and pharmacology [20][21][22][23][24][25][26] have recently been resumed in many excellent reviews. This contribution focuses on the development of clinical candidates and the multifaceted potential indications targeted.In mammalian brain histaminergic neurons originate in the tuberomammillary nucleus (TMN) spreading into above mentioned brain regions, where they control histamine levels by regulation of synthesis and liberation rates 27) and modulate different neuronal systems. 28) H 3 R expression is not solely restricted to histaminergic neurons: due to its function as a heteroreceptor it can be found on colocalised neurons, and H 3 R activation modulates the release of various important neurotransmitters, i.e. dopamine, [29][30][31][32][33] acetylcholine, [34][35][36][37] norepinephrine, 38,39) serotonin, 40,41) GABA, [42][43][44] glutamate, 45) and substance P. [46][47][48] Therefore, histaminergic neurons and the cross-linkage between major neurotransmitter systems are involved in many (patho)physiological brain functions, including vigilance, memory processes, feeding behaviour and locomotor activity (Fig. 2). Interneuron cross-talk and adaptive processes seem to be important factors in H 3 Rmediated signalling. Molecular AspectsThe human histamine H 3 receptor (hH 3 R) cDNA firstly described 1999 encodes a 445 amino acid protein and belongs to the his...

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“…Histamine has been shown to enhance hippocampal NMDA receptor currents (Bekkers, 1993;Vorobjev et al, 1993;Brown et al, 1995). LTP of the Schaffer collateral (presumed apical dendritic) synapses in CA1 in vitro was reduced in H 1 and H 2 receptor gene knock-out mice (Dai et al, 2007), but potentiation of population spikes was enhanced in mice lacking histidine decarboxylase, the enzyme responsible for the synthesis of histamine (Liu et al, 2007).…”

Section: Ltp and Histaminementioning

confidence: 99%

Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking

Luo

Leung²

2010

Journal of Neuroscience

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Long-term potentiation (LTP) in hippocampal CA1 depends on the behavioral state of LTP induction. We hypothesize that histaminergic activity in the septohippocampal system, which is active during walking compared with other behavioral states, is responsible for the behavioral dependence of LTP. Field basal-dendritic EPSPs of CA1 pyramidal cells were recorded in freely behaving rats, and LTP was induced by a single 200 Hz stimulation train (0.5 s duration). Basal-dendritic LTP was facilitated when induced during walking compared with awake immobility (IMM) or rapid-eye-movement sleep. The facilitation of basal-dendritic LTP during walking was abolished by lesion of tuberomammillary nucleus (TMN) neurons with orexin-saporin or by intramedial-septal infusion of the H 1 histaminergic blocker triprolidine but not the H 2 histaminergic blocker cimetidine. Conversely, histamine infusion in the medial septum enhanced the basal-dendritic LTP induced during IMM to a magnitude similar to that induced during walking. Basal-dendritic LTP induced during walking was not further enhanced by intraseptal histamine infusion. Combined with the previous result that behavior-dependent LTP is mediated by cholinergic septohippocampal neurons, we conclude that the facilitation of basal-dendritic LTP in CA1 during walking was mediated by TMN histaminergic afferents acting on H 1 receptors in the medial septum, which may then enhance cholinergic and noncholinergic inputs to the hippocampus.

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Selective cognitive dysfunction in mice lacking histamine H1 and H2 receptors

Cited by 116 publications

References 45 publications

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

Histamine H3 Receptor Antagonists Go to Clinics

Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking

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