| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2493521 | Neuropharmacology | 2012 | 11 Pages |
Alcohol drinking during adolescence can induce long-lasting effects on the motivation to consume alcohol. Abnormal plasticity in reward-related processes might contribute to the vulnerability of adolescents to drug addiction. We have shown that binge-like ethanol treatment in adolescent rats induces alterations in the dopaminergic system and causes histone modifications in brain reward regions. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced alterations in gene expression and behavior, we addressed the hypothesis that ethanol is capable of inducing transcriptional changes by histone modifications in specific gene promoters in adolescent brain reward regions, and whether these events are associated with acquisition of place conditioning. After treating juvenile and adult rats with intermittent ethanol administration, we found that ethanol treatment upregulates histone acetyl transferase (HAT) activity in adolescent prefrontal cortex and increases histone (H3 or H4) acetylation and H3(K4) dimethylation in the promoter region of cFos, Cdk5 and FosB. Inhibition of histone deacetylase by sodium butyrate before ethanol injection enhances both up-regulation of HAT activity and histone acetylation of cFos, Cdk5 and FosB. Furthermore, co-administration of sodium butyrate with ethanol prolongs the extinction of conditioned place aversion and increased the reinstatement effects of ethanol in ethanol-treated adolescents, but not in ethanol-treated adult rats. These results indicate that ethanol exposure during adolescence induces chromatin remodeling, changes histone acetylation and methylation, and modify the effects of ethanol on place conditioning. They also suggest that epigenetic mechanisms might open up avenues to new treatments for binge drinking-induced drug addiction during adolescence.
► Ethanol treatment during adolescence induces changes in histone acetylation. ► Ethanol affects the promoter region of cFos, Cdk5 and FosB in the prefrontal cortex. ► Epigenetic changes are associated with ethanol-induced long-term place conditioning.
