Histamine and H3 receptor-dependent mechanisms regulate ethanol stimulation and conditioned place preference in mice

Nuutinen, Saara; Karlstedt, Kaj; Aitta-aho, Teemu; Korpi, Esa R.; Panula, Pertti

doi:10.1007/s00213-009-1710-5

Cited by 42 publications

(49 citation statements)

References 62 publications

(86 reference statements)

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“…However, changes in the DA neuron activity do not necessarily produce a response in DA release, and it is also possible that different mesolimbic VTA DA neuron populations separately mediate rewarding and aversive behaviors (Lammel et al, 2011). Indeed, repeated GAN administrations in an unbiased place-conditioning paradigm resulted in aversion rather than preference for conditioned floors in C57BL/6J mice, with which we have previously seen significant morphine-and ethanol-induced conditioned preference Nuutinen et al, 2010). Further, we have found that THIP induces prolonged conditioned aversion in mice and that it fails to sustain reinforcement behavior in baboons, in contrast to benzodiazepines (Vashchinkina et al, 2012).…”

Section: Failure To Induce a Cppmentioning

confidence: 94%

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Vashchinkina

Manner

Vekovischeva

et al. 2013

Neuropsychopharmacol

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The main fast-acting inhibitory receptors in the mammalian brain are g-aminobutyric acid type-A (GABA A ) receptors for which neurosteroids, a subclass of steroids synthesized de novo in the brain, constitute a group of endogenous ligands with the most potent positive modulatory actions known. Neurosteroids can act on all subtypes of GABA A receptors, with a preference for d-subunitcontaining receptors that mediate extrasynaptic tonic inhibition. Pathological conditions characterized by emotional and motivational disturbances are often associated with perturbation in the levels of endogenous neurosteroids. We studied the effects of ganaxolone (GAN)-a synthetic analog of endogenous allopregnanolone that lacks activity on nuclear steroid receptors-on the mesolimbic dopamine (DA) system involved in emotions and motivation. A single dose of GAN in young mice induced a dose-dependent, longlasting neuroplasticity of glutamate synapses of DA neurons ex vivo in the ventral tegmental area (VTA). Increased a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate ratio and rectification of AMPA receptor responses even at 6 days after GAN administration suggested persistent synaptic targeting of GluA2-lacking AMPA receptors. This glutamate neuroplasticity was not observed in GABA A receptor d-subunit-knockout (d-KO) mice. GAN (500 nM) applied locally to VTA selectively increased tonic inhibition of GABA interneurons and triggered potentiation of DA neurons within 4 h in vitro. Place-conditioning experiments in adult wild-type C57BL/6J and d-KO mice revealed aversive properties of repeated GAN administration that were dependent on the d-subunits. Prolonged neuroadaptation to neurosteroids in the VTA might contribute to both the physiology and pathophysiology underlying processes and changes in motivation, mood, cognition, and drug addiction.

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Section: Failure To Induce a Cppmentioning

confidence: 94%

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Vashchinkina

Manner

Vekovischeva

et al. 2013

Neuropsychopharmacol

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“…CPP paradigm was used as described in (Nuutinen et al, 2010a) and it followed the principles of an unbiased, fully counterbalanced conditioning described by (Cunningham et al, 2006). Conditioning cages were individual transparent plastic cages (42 Â 26 Â 20 cm) covered with clear plastic lids with ventilation holes.…”

Section: Alcohol-induced Cppmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Treatment with H3R antagonists suppresses alcohol drinking in alcohol-preferring rats (Lintunen et al, 2001;Galici et al, 2010) and inhibits alcohol reward in a conditioned place preference (CPP) paradigm in mice (Nuutinen et al, 2010a). The H3R antagonists themselves are not rewarding or aversive (Nuutinen et al, 2010a;Munzar et al, 2004). 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.…”

Section: Introductionmentioning

confidence: 99%

“…Mice lacking histamine synthetizing enzyme, histidine decarboxylase are not stimulated by alcohol (Nuutinen et al, 2010a) and H3R antagonists increase the stimulatory response by alcohol in DBA/2J mice (Nuutinen et al, 2010b) and decrease it in C57BL/6Sca mice (Nuutinen et al, 2010a). Further, rats with high tolerance to alcohol show impaired performance on a tilting plane motor function test in response to a-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase (Lintunen et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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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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Therapeutic Potential of Histamine H3 Receptors in Substance Use Disorders

Ciano

Hendershot

Foll

2022

The Functional Roles of Histamine Receptors

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Histamine and H3 receptor-dependent mechanisms regulate ethanol stimulation and conditioned place preference in mice

Cited by 42 publications

References 62 publications

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

Neurosteroid Agonist at GABAA Receptor Induces Persistent Neuroplasticity in VTA Dopamine Neurons

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

Therapeutic Potential of Histamine H3 Receptors in Substance Use Disorders

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