Activation of metabotropic glutamate (mGlu)2 receptors suppresses histamine release in limbic brain regions following acute ketamine challenge

Fell, Matthew; Katner, Jason; Johnson, Bryan G.; Khilevich, Albert; Schkeryantz, Jeffrey M.; Perry, Kenneth W.; Svensson, Kjell

doi:10.1016/j.neuropharm.2009.11.014

Cited by 30 publications

(31 citation statements)

References 35 publications

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“…Thus, histaminergic participation in reconsolidation would necessarily depend upon the occurrence of some changes in NMDA activity, whereas that involved in consolidation would not, both neurotransmitter systems acting individually as well as interactively on both cognitive processes. At first sight, these possibilities are not easy to reconcile with the findings that NMDA receptor blockade can augment and metabotropic (mGlu) 2 receptor activation can mitigate histamine neuron activity in the mouse and rat prefrontal cortex and especially ventral hippocampus, histamine neurons expressing NMDA receptors (Faucard et al, 2006;Fell et al, 2010). One must admit that dizocilpne-induced histamine activation either occurs in brain areas that are not involved in memory mechanisms or it is not enough to be able to influence these processes in presence of an overwhelming NMDA receptor blockade.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of histamine H3 receptor inverse agonist thioperamide, given alone or in combination with the N-methyl-d-aspartate receptor antagonist dizocilpine, on reconsolidation and consolidation of a contextual fear memory in mice

Charlier

Tirelli

2011

Neuroscience

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Abstract-Albeit there is no doubt that histamine and its H 3 receptors participate in several aspects of learning and memory, such as memory consolidation, nothing is known about their potential involvement in memory reconsolidation. On the basis of previous reports of pro-cognitive effects of histamine H 3 receptor inverse agonists (which augment histamine release), we investigated to what extent the most representative of them, thioperamide, is able to facilitate reconsolidation of a contextually-conditioned fear memory in C57BL/6J mice. We also examined the effects of thioperamide on the stark disruptive effect that the non-competitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine (MK-801) typically exerts on both reconsolidation and consolidation. Post-training systemic injections (i.p.) of thioperamide facilitated consolidation at 10 and 20 mg/kg and reversed amnesia induced by an i.p. injection of 0.12 mg/kg dizocilpine at 5, 10 and 20 mg/kg. Importantly, none of the five thioperamide doses (2.5, 5, 10, 20 and 30 mg/kg) given right after reactivation (reexposure to the context in which training took place 48 h earlier) affected reconsolidation, whereas all similarly given doses of dizocilpine (0.03, 0.06 and 0.12 mg/kg) disrupted it more or less equally. By contrast, thioperamide was able to unambiguously reverse the deficit in reconsolidation induced by 0.12 mg/kg dizocilpine at 10 and 20, but not 5 mg/kg. This is the first demonstration of an involvement of the interactive articulation between histamine and NMDA receptors in the mechanisms of memory reconsolidation, which seems to be indifferent to an increase of brain histamine per se. The results suggest a qualitatively different participation of histaminergic signalling in the mechanisms of reconsolidation and consolidation. The precise circuits within which these interactions take place are yet to be identified.

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Section: Discussionmentioning

confidence: 99%

Differential effects of histamine H3 receptor inverse agonist thioperamide, given alone or in combination with the N-methyl-d-aspartate receptor antagonist dizocilpine, on reconsolidation and consolidation of a contextual fear memory in mice

Charlier

Tirelli

2011

Neuroscience

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“…Although not reported here, we did not observe any effects of THIIC on extracellular (or brain tissue) monoamine levels (dopamine, serotonin, and norepinephrine) or their metabolites. Based on the finding that THIIC has significant sleep-promoting effects and that we observed significant interactions for CBiPES with the histamine system (Fell et al, 2010), we assessed the effects of THIIC on extracellular histamine levels. THIIC clearly attenuated the increase in extracellular histamine in the mPFC, which occurs during the dark phase, suggesting that potentiation of mGlu2 receptor activity can modulate central histaminergic neurotransmission in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Implantation of a BAS guide cannula into the mPFC [anterior (A) 3.2 mm; lateral (L) 0.8 mm; and ventral (V), -2 mm] was carried out by Taconic Farms (Germantown, NY) 5 to 7 days before the experiment as described previously (Fell et al, 2010). A concentric type probe (BR-4) from BAS Bioanalytical Systems (West Lafayette, IN) to match the implanted cannula with a 4-mm membrane tip extending below the cannula was flushed with water and carefully inserted through the cannula 16 h before the experiment began.…”

Section: In Vivo Neurochemistrymentioning

confidence: 99%

N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a Novel Metabotropic Glutamate 2 Potentiator with Potential Anxiolytic/Antidepressant Properties: In Vivo Profiling Suggests a Link between Behavioral and Central Nervous System Neurochemical Changes

Fell

Witkin²,

Falcone³

et al. 2010

J Pharmacol Exp Ther

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The normalization of excessive glutamatergic neurotransmission through the activation of metabotropic glutamate 2 (mGlu2) receptors may have therapeutic potential in a variety of psychiatric disorders, including anxiety/depression and schizophrenia. Here, we characterize the pharmacological properties of N- (4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a structurally novel, potent, and selective allosteric potentiator of human and rat mGlu2 receptors (EC 50 ϭ 23 and 13 nM, respectively). THIIC produced anxiolytic-like efficacy in the rat stress-induced hyperthermia assay and the mouse stress-induced elevation of cerebellar cGMP and marble-burying assays. THIIC also produced robust activity in three assays that detect antidepressant-like activity, including the mouse forced-swim test, the rat differential reinforcement of low rate 72-s assay, and the rat dominant-submissive test, with a maximal response similar to that of imipramine. Effects of THIIC in the forced-swim test and marble burying were deleted in mGlu2 receptor null mice. Analysis of sleep electroencephalogram (EEG) showed that THIIC had a sleeppromoting profile with increased non-rapid eye movement (REM) and decreased REM sleep. THIIC also decreased the dark phase increase in extracellular histamine in the medial prefrontal cortex and decreased levels of the histamine metabolite tele-methylhistamine (t-MeHA) in rat cerebrospinal fluid. Collectively, these results indicate that the novel mGlu2-positive allosteric modulator THIIC has robust activity in models used to predict anxiolytic/antidepressant efficacy, substantiating, at least with this molecule, differentiation in the biological impact of mGlu2 potentiation versus mGlu2/3 orthosteric agonism. In addition, we provide evidence that sleep EEG and CSF t-MeHA might function as viable biomarker approaches to facilitate the translational development of THIIC and other mGlu2 potentiators.

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“…On the other hand, Fell et al (27) reported that activation of mGlu2 receptor (Group II mGlu receptors subtype) suppressed the histamine release in the limbic area, hippocampus, medial prefrontal cortex, and so on. This effect might be also be involved in inefficacy of hippocampal APDC for pyrilamine-induced memory deficit.…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of a Hippocampal Metabotropic Glutamate– Receptor Agonist on Histamine H1 Receptor Antagonist–Induced Memory Deficit in Rats

2010

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Abstract. This study was performed to investigate the ameliorative effects of metabotropic glutamate (mGlu)-receptor agonists on histamine H 1 receptor antagonist-induced spatial memory deficit and the decrease in hippocampal theta activity in rats. Intraperitoneal injection of pyrilamine (35 mg/kg) resulted in impaired reference and working memory in the radial maze task and decreased hippocampal theta amplitude and power. The working memory deficit and decreased hippocampal theta power induced by pyrilamine were ameliorated by intrahippocampal injection of ( RS )-3,5-dihydroxyphenylglycine (DHPG) (1 and 10 μ g/side), a group I mGlu-receptor agonist; however, intrahippocampal injection of (2 R ,4 R )-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGlu-receptor agonist, and L -(+)-2-amino-4-phosphonobutyric acid ( L -AP4), a group III mGlu-receptor agonist, showed no significant effect on the pyrilamine-induced memory deficit and decreased hippocampal theta activity. These results indicate that the activation of hippocampal group Ι mGlu receptors, but not group II and III mGlu receptors, improve the histamine H 1 receptor antagonist-induced working memory deficit and decreased hippocampal theta activity.

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Activation of metabotropic glutamate (mGlu)2 receptors suppresses histamine release in limbic brain regions following acute ketamine challenge

Cited by 30 publications

References 35 publications

Differential effects of histamine H3 receptor inverse agonist thioperamide, given alone or in combination with the N-methyl-d-aspartate receptor antagonist dizocilpine, on reconsolidation and consolidation of a contextual fear memory in mice

Differential effects of histamine H3 receptor inverse agonist thioperamide, given alone or in combination with the N-methyl-d-aspartate receptor antagonist dizocilpine, on reconsolidation and consolidation of a contextual fear memory in mice

Ameliorative Effect of a Hippocampal Metabotropic Glutamate– Receptor Agonist on Histamine H1 Receptor Antagonist–Induced Memory Deficit in Rats

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