JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats.
Psychopharmacology (Berl)
; 214(4): 829-41, 2011 Apr.
Article
in En
| MEDLINE
| ID: mdl-21086115
ABSTRACT
RATIONALE A few recent studies suggest that brain histamine levels and signaling via H(3) receptors play an important role in modulation of alcohol stimulation and reward in rodents. OBJECTIVE:
The present study characterized the effects of a novel, selective, and brain penetrant H(3) receptor antagonist (JNJ-39220675) on the reinforcing effects of alcohol in rats.METHODS:
The effect of JNJ-39220675 on alcohol intake and alcohol relapse-like behavior was evaluated in selectively bred alcohol-preferring (P) rats using the standard two-bottle choice method. The compound was also tested on operant alcohol self administration in non-dependent rats and on alcohol-induced ataxia using the rotarod apparatus. In addition, alcohol-induced dopamine release in the nucleus accumbens was tested in freely moving rats.RESULTS:
Subcutaneous administration of the selective H(3) receptor antagonist dose-dependently reduced both alcohol intake and preference in alcohol-preferring rats. JNJ-39220675 also reduced alcohol preference in the same strain of rats following a 3-day alcohol deprivation. The compound significantly and dose-dependently reduced alcohol self-administration without changing saccharin self-administration in alcohol non-dependent rats. Furthermore, the compound did not change the ataxic effects of alcohol, alcohol elimination rate, nor alcohol-induced dopamine release in nucleus accumbens.CONCLUSIONS:
These results indicate that blockade of H(3) receptor should be considered as a new attractive mechanism for the treatment of alcoholism.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridines
/
Azepines
/
Alcoholism
/
Histamine H3 Antagonists
Limits:
Animals
Language:
En
Journal:
Psychopharmacology (Berl)
Year:
2011
Document type:
Article
Affiliation country: