JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats.

Published

Journal Article

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

Duke Authors

Cited Authors

  • Galici, R; Rezvani, AH; Aluisio, L; Lord, B; Levin, ED; Fraser, I; Boggs, J; Welty, N; Shoblock, JR; Motley, ST; Letavic, MA; Carruthers, NI; Dugovic, C; Lovenberg, TW; Bonaventure, P

Published Date

  • April 2011

Published In

Volume / Issue

  • 214 / 4

Start / End Page

  • 829 - 841

PubMed ID

  • 21086115

Pubmed Central ID

  • 21086115

Electronic International Standard Serial Number (EISSN)

  • 1432-2072

Digital Object Identifier (DOI)

  • 10.1007/s00213-010-2092-4

Language

  • eng

Conference Location

  • Germany