Back to Search
Start Over
Histamine H3 receptor antagonist decreases cue-induced alcohol reinstatement in mice.
- Source :
-
Neuropharmacology [Neuropharmacology] 2016 Jul; Vol. 106, pp. 156-63. Date of Electronic Publication: 2015 Jun 21. - Publication Year :
- 2016
-
Abstract
- We have earlier found that the histamine H3 receptor (H3R) antagonism diminishes motivational aspects of alcohol reinforcement in mice. Here we studied the role of H3Rs in cue-induced reinstatement of alcohol seeking in C57BL/6J mice using two different H3R antagonists. Systemic administration of H3R antagonists attenuated cue-induced alcohol seeking suggesting that H3R antagonists may reduce alcohol craving. To understand how alcohol affects dopamine and histamine release, a microdialysis study was performed on C57BL/6J mice and the levels of histamine, dopamine and dopamine metabolites were measured in the nucleus accumbens. Alcohol administration was combined with an H3R antagonist pretreatment to reveal whether modulation of H3R affects the effects of alcohol on neurotransmitter release. Alcohol significantly increased the release of dopamine in the nucleus accumbens but did not affect histamine release. Pretreatment with H3R antagonist ciproxifan did not modify the effect of alcohol on dopamine release. However, histamine release was markedly increased with ciproxifan. In conclusion, our findings demonstrate that H3R antagonism attenuates cue-induced reinstatement of alcohol seeking in mice. Alcohol alone does not affect histamine release in the nucleus accumbens but H3R antagonist instead increases histamine release significantly suggesting that the mechanism by which H3R antagonist inhibits alcohol seeking found in the present study and the decreased alcohol reinforcement, reward and consumption found earlier might include alterations in the histaminergic neurotransmission in the nucleus accumbens. These findings imply that selective antagonists of H3Rs could be a therapeutic strategy to prevent relapse and possibly diminish craving to alcohol use. This article is part of the Special Issue entitled 'Histamine Receptors'.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Alcohol Drinking drug therapy
Alcohol Drinking metabolism
Alcohol-Related Disorders metabolism
Animals
Azepines pharmacology
Conditioning, Operant drug effects
Conditioning, Operant physiology
Cues
Disease Models, Animal
Dopamine metabolism
Dose-Response Relationship, Drug
Drug-Seeking Behavior physiology
Extinction, Psychological drug effects
Extinction, Psychological physiology
Histamine metabolism
Imidazoles pharmacology
Male
Mice, Inbred C57BL
Nucleus Accumbens drug effects
Nucleus Accumbens metabolism
Pyridines pharmacology
Receptors, Histamine H3 metabolism
Self Administration
Alcohol Deterrents pharmacology
Alcohol-Related Disorders drug therapy
Drug-Seeking Behavior drug effects
Histamine H3 Antagonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 106
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26107118
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2015.06.006