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Long‐lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol
Author(s) -
Rimondini Roberto,
Arlinde Christina,
Sommer Wolfgang,
Heilig Markus
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0593com
Subject(s) - monoaminergic , glutamatergic , ethanol , amygdala , alcohol use disorder , endocannabinoid system , neurotoxicity , neuroscience , craving , alcohol dependence , alcohol , addiction , medicine , psychology , chemistry , glutamate receptor , toxicity , receptor , biochemistry , serotonin
Prolonged exposure of the brain to ethanol is a prerequisite for developing ethanol dependence, but the underlying neural adaptations are unknown. Here we demonstrate that rats subjected to repeated cycles of intoxication and withdrawal develop a marked and long‐lasting increase in voluntary ethanol intake. Exposure‐induced but not spontaneous alcohol intake is antagonized by acamprosate, a compound clinically effective in human alcoholism. Expression analysis of cingulate cortex and amygdala reveals a set of long‐term up‐regulated transcripts in this model. These include members of pathways previously implicated in alcohol dependence (glutamatergic, endocan‐nabinoid, and monoaminergic neurotransmission), as well as pathways not previously thought to be involved in this disorder (e.g., members of the mitogen‐activated protein kinase pathway). Thus, alternating periods of ethanol intoxication and withdrawal are sufficient to induce an altered functional brain state, which is likely to be encoded by long‐term changes in gene expression. These observations may have important implications for how alcoholism is managed clinically. Novel clinically effective treatments may be possible to develop by targeting the products of genes found to be regulated in our model.—Rimondini, R., Arlinde, C., Sommer, W., Heilig, M. Long‐lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. FASEB J. 16, 27–35 (2002)