Effects of the H3 receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions

Brabant, Christian; Alleva, Livia; Grisar, Thierry; Quertemont, Étienne; Lakaye, Bernard; Ohtsu, Hiroshi; Lin, Jian‐Sheng; Jatlow, Peter; Picciotto, Marina R.; Tirelli, Ezio

doi:10.1007/s00213-008-1345-y

Cited by 48 publications

(41 citation statements)

References 41 publications

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“…H3R antagonists modulate also the effects of other drugs such as cocaine (Brabant et al, 2005(Brabant et al, , 2006(Brabant et al, , 2009Clapham and Kilpatrick, 1994) and amphetamine (Munzar et al, 1998(Munzar et al, , 2004. However, one of the probable mechanisms underlying the changes in cocaine responses might be the interaction of the imidazole-based H3R antagonists with the liver cytochrome P-450 enzymes resulting in higher concentration of cocaine in the blood (Brabant et al, 2009). We have not detected H3R ligand-induced alterations in plasma alcohol concentrations suggesting that H3R antagonism could be beneficial in the treatment of alcoholism.…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Role of Histamine H3 Receptor in Alcohol Consumption and Alcohol Reward in Mice

Nuutinen

Lintunen

Vanhanen

et al. 2011

Neuropsychopharmacol

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Recent research suggests that histamine H3 receptor (H3R) antagonism may diminish motivational aspects of alcohol dependence. We studied the role of H3Rs in alcohol-related behaviors using H3R knockout (KO) mice and ligands. H3R KO mice consumed less alcohol than wild-type (WT) mice in a two-bottle free-choice test and in a 'drinking in the dark' model. H3R antagonist ciproxifan suppressed and H3R agonist immepip increased alcohol drinking in C57BL/6J mice. Impairment in reward mechanisms in H3R KO mice was confirmed by the lack of alcohol-evoked conditioned place preference. Plasma alcohol concentrations of H3R KO and WT mice were similar. There were no marked differences in brain biogenic amine levels in H3R KO mice compared with the control animals after alcohol drinking. In conclusion, the findings of this study provide evidence for the role of H3R receptor in alcohol-related behaviors, especially in alcohol drinking and alcohol reward. Thus, targeting H3Rs with a specific antagonist might be a potential means to treat alcoholism in the future.

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Section: Introductionmentioning

confidence: 99%

Evidence for the Role of Histamine H3 Receptor in Alcohol Consumption and Alcohol Reward in Mice

Nuutinen

Lintunen

Vanhanen

et al. 2011

Neuropsychopharmacol

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“…We repeated the experiment with another H3 agonist, immepip (39). Administration of SKF82958 and immepip (20 mg/kg) produced the same pattern of results as RAMH.…”

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confidence: 98%

The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons

Rapanelli¹,

Frick²,

Horn³

et al. 2016

Journal of Biological Chemistry

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The basal ganglia have a central role in motor patterning, habits, motivated behaviors, and cognition as well as in numerous neuropsychiatric disorders. Receptors for histamine, especially the H3 receptor (H3R), are highly expressed in the striatum, the primary input nucleus of the basal ganglia, but their effects on this circuitry have been little explored. H3R interacts with dopamine (DA) receptors ex vivo; the nature and functional importance of these interactions in vivo remain obscure. We found H3R activation with the agonist R-(-)-␣-methylhistamine to produce a unique time-and cell type-dependent profile of molecular signaling events in the striatum. H3 agonist treatment did not detectably alter extracellular DA levels or signaling through the cAMP/DARPP-32 signaling pathway in either D1-or D2-expressing striatal medium spiny neurons (MSNs). In D1-MSNs, H3 agonist treatment transiently activated MAPK signaling and phosphorylation of rpS6 and led to phosphorylation of GSK3␤-Ser 9 , a novel effect. Consequences of H3 activation in D2-MSNs were completely different. MAPK signaling was unchanged, and GSK3␤-Ser 9 phosphorylation was reduced. At the behavioral level, two H3 agonists had no significant effect on locomotion or stereotypy, but they dramatically attenuated the locomotor activation produced by the D1 agonist SKF82958. H3 agonist co-administration blocked the activation of MAPK signaling and the phosphorylation of rpS6 produced by D1 activation in D1-MSNs, paralleling behavioral effects. In contrast, GSK3␤-Ser 9 phosphorylation was seen only after H3 agonist treatment, with no interactive effects. H3R signaling has been neglected in models of basal ganglia function and has implications for a range of pathophysiologies.The basal ganglia play a critical role in the regulation of cognition, motor control, motivated behavior, and habit learning as well as in the pathophysiology of a range of neuropsychiatric conditions, including Parkinson's disease, Tourette syndrome, and drug addiction (1-6). Factors that modulate information flow through the basal ganglia circuitry are therefore of broad importance. The roles of dopamine (DA) 4 and acetylcholine in the regulation of striatal information processing have been extensively studied. Histamine (HA) is produced in the tuberomamillary nucleus of the posterior hypothalamus; these neurons project broadly throughout the brain, including to the striatum (7). HA receptors are prominent throughout the basal ganglia (7,8), but their function in modulating this circuitry is not well understood, and very few studies have examined their functional importance in vivo (9).The striatum (equivalent to the caudate and putamen in primates) is the largest nucleus of the basal ganglia and the primary site of cortical and thalamic input. Its principal cells, the medium spiny neurons (MSNs), can be divided into two subpopulations based on their projections. Striatonigral or "direct pathway" neurons preferentially express the D1 DA receptor and have a net disinhibitory effect on t...

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“…One study found enhanced PPI following administration of both thioperamide and ciproxifan in DBA/2 mice, but not in C57BL/6 mice (Browman et al, 2004). Thus, the role of H3R in PPI seems to be dependent on both the mouse strain and the use of imidazole-based H3R antagonists, which affect liver CYP450 metabolism (Brabant et al, 2009). Thus, when administered in combination with drugs, using the same route of metabolism, increased/decreased concentrations of the drugs in the blood can be detected.…”

Section: H3r Regulates Sensorimotor Gating and Dopaminergic Signalingmentioning

confidence: 99%

Histamine H3 Receptor Regulates Sensorimotor Gating and Dopaminergic Signaling in the Striatum

Kononoff

Nuutinen

Tuominen

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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The brain histamine system has been implicated in regulation of sensorimotor gating deficits and in Gilles de la Tourette syndrome. Histamine also regulates alcohol reward and consumption via H3 receptor (H3R), possibly through an interaction with the brain dopaminergic system. Here, we identified the histaminergic mechanism of sensorimotor gating and the role of histamine H3R in the regulation of dopaminergic signaling. We found that H3R knockout mice displayed impaired prepulse inhibition (PPI), indicating deficiency in sensorimotor gating. Histamine H1 receptor knockout and histidine decarboxylase knockout mice had similar PPI as their controls. Dopaminergic drugs increased PPI of H3R knockout mice to the same level as in control mice, suggesting that changes in dopamine receptors might underlie deficient PPI response when H3R is lacking. Striatal dopamine D1 receptor mRNA level was lower, and D1 and D2 receptor-mediated activation of extracellular signalregulated kinase 1/2 was absent in the striatum of H3R knockout mice, suggesting that H3R is essential for the dopamine receptor-mediated signaling. In conclusion, these findings demonstrate that H3R is an important regulator of sensorimotor gating, and the lack of H3R significantly modifies striatal dopaminergic signaling. These data support the usefulness of H3R ligands in neuropsychiatric disorders with preattentional deficits and disturbances in dopaminergic signaling.

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Effects of the H3 receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions

Cited by 48 publications

References 41 publications

Evidence for the Role of Histamine H3 Receptor in Alcohol Consumption and Alcohol Reward in Mice

Evidence for the Role of Histamine H3 Receptor in Alcohol Consumption and Alcohol Reward in Mice

The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons

Histamine H3 Receptor Regulates Sensorimotor Gating and Dopaminergic Signaling in the Striatum

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