The histaminergic H1, H2, and H3 receptors of the lateral septum differentially mediate the anxiolytic-like effects of histamine on rats' defensive behaviors in the elevated plus maze and novelty-induced suppression of feeding paradigm

3区 · 医学

Article

作者: Menard, Janet L. ; Chee, San-San A.

The neural histaminergic system is involved in a wide range of physiological processes, including anxiety. Histaminergic neurons are localized in the tuberomammillary nucleus of the posterior hypothalamus and share bidirectional connections with the lateral septum, an area well implicated in anxiety. The current study examined whether the histaminergic system of the lateral septum regulates rats' defensive behaviors in two animal models of anxiety, the elevated plus maze (EPM) and novelty-induced suppression of feeding paradigm (NISF). We found that bilateral infusions of histamine (1.0 μg and 5.0 μg) into the lateral septum selectively decreased rats' defensive behaviors in the EPM (both doses) and NISF (1.0 μg only). Follow-up studies found that pre-infusions of the H1 and H2 antagonists, pyrilamine (20 μg) and ranitidine (20 μg) respectively, reversed the anxiolytic-like effects of intra-LS histamine (1.0 μg) in the NISF but not in the EPM, while pre-infusions of the H3 antagonist ciproxifan (200 pg) attenuated the anxiolytic-like effects of intra-LS histamine in the EPM but not in the NISF. This double dissociation suggests that H1 and H2 receptors in the lateral septum, likely via a post-synaptic mechanism, mediate the anxiolytic-like effects of histamine in the NISF but not in the EPM. In contrast, lateral septal H3 receptors mediate, likely pre-synaptically, the anxiolytic-like effects of histamine in the EPM but not in the NISF. Our findings indicate that these receptors differentially contribute to rats' specific defensive behaviors in the EPM and NISF, that is, avoidance of open spaces and neophagia respectively.

2009-08-01·Psychopharmacology3区 · 医学

Anxiolytic-like profiles of histamine H3 receptor agonists in animal models of anxiety: a comparative study with antidepressants and benzodiazepine anxiolytic

3区 · 医学

Article

作者: Masayo Oyama ; Rie Shinei ; Fumikazu Yokoyama ; Takako Nagayama ; Yasuo Sato ; Makoto Ishikawa ; Miki Yamauchi ; Kunihiro Okuma ; Kaname Onozawa ; Nobukazu Kakui

RATIONALEHistamine H3 receptor functions as a presynaptic auto- and hetero-receptor on histaminergic and non-histaminergic neurons in the brain regulating the synaptic release of numerous neurotransmitters. Therefore, the ligands for this receptor have been proposed to be of therapeutic interest for the treatment of various neuropsychiatric disorders. At present, however, the psychopharmacological profiles of H3 ligands, particularly H3 agonists, have not been extensively studied.OBJECTIVEThe present study investigated the anxiolytic-like profiles of H3-selective agonists in a variety of classical (benzodiazepine-sensitive) and atypical (antidepressant-effective) animal models of anxiety. Comparator drugs used were diazepam and both fluvoxamine and desipramine in the former and latter models, respectively.RESULTSH3 agonist R-alpha-methylhistamine and immepip were inactive in rat elevated plus maze test and Vogel type conflict test where diazepam (5 mg/kg) produced significant anxiolytic-like effects. Meanwhile, these H3 agonists (10-30 mg/kg) significantly reduced isolation-induced vocalizations in guinea pig pups and isolation-induced aggressive behavior in mouse resident-intruder test. Moreover, in rat conditioned fear stress test, R-alpha-methylhistamine (30 mg/kg) and immepip (10 mg/kg) significantly decreased freezing time, which were completely reversed by concomitant treatment with H3 antagonist, thioperamide (10 mg/kg). In contrast to the limited efficacy obtained with desipramine (30 mg/kg), fluvoxamine (20-60 mg/kg) exhibited anxiolytic-like effects in all the latter three atypical models.CONCLUSIONSThese data suggest that the H3 agonists may have anxiolytic-like effects similar to those of selective serotonin reuptake inhibitors but not benzodiazepine anxiolytics and represent a novel strategy for the treatment of some anxiety disorders in which selective serotonin reuptake inhibitors are prescribed.

2007-10-01·Journal of Neurochemistry2区 · 医学

Reduced histamine levels and H₃ receptor antagonist‐induced histamine release in the amygdala of Apoe−/− mice

2区 · 医学

Article

作者: Pfankuch, Tim ; Raber, Jacob ; van Meer, Peter

AbstractThe histamine H3 receptor is a constitutively active G protein‐coupled receptor for the neurotransmitter histamine that serves a negative feedback function. A role for the histamine H3 receptor has been suggested in neurodegenerative diseases, such as Parkinsons disease and Alzheimer’s disease. Mice deficient in apolipoprotein E (apoE), a protein involved in development, regeneration, neurite outgrowth, and neuroprotection, show increased measures of anxiety and reduced sensitivity to effects of histamine H3 receptor antagonists on measures of anxiety. In this study, we tested whether in mice lacking apoE (Apoe−/−) histamine levels and histamine release in brain areas involved in the regulation of anxiety are altered. H3 receptor antagonist‐induced histamine release was lower in the amygdala of Apoe−/− than wild‐type mice. In contrast, there were no genotype differences in histamine release in the hypothalamus. Consistent with these data, histamine immunohistochemistry revealed lower total and synaptic histamine levels in the central nucleus of the amygdala of Apoe−/− than wild‐type mice. Such changes were not seen in the hypothalamus, hippocampus, or cortex. In Apoe−/− mice, chronically decreased histamine levels and reduced histamine release in the amygdala might contribute to increased measures of anxiety.

100 项与 H3 receptor antagonists(Gedeon Richter Pharma) 相关的药物交易

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