Rat Cocaine Addiction And Relapse Of Ambush Every Nuclear Histone Acetylation Levels And The Group Of Histone Deacetylase Inhibitor Sodium Butyrate On The Addictive Behavior

The mechanisms of cocaine addiction are very obscure and complicated. Abnormality of gene expression is one of the most important mechanisms involved in a state of addiction caused by drugs of abuse. However, the distinct molecular mechanisms that control gene expression are complicated.Chromatin remodeling is a crucial step prior to transcription initiation. One of chromatin regulatory factors histone acetylation-deacetylation is reversible and stringently controlled by 2 large groups of enzymes: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Acetylation of histones H3 and H4, as well as phosphoacetylation of H3, at gene promoters is linked to increased gene activity, while deacetylation is linked with suppression and silencing of gene activity. Recently, histone modification and cocaine induced neural plasticity have been linked in many studies. But the accurate role of histone acetylation playing in cocaine addiction is still open to doubt. In this study, we used immunohistochemistry to detect the condition of histone acetylation during the process of cocaine self-administration in rats'nucleus accumbens which is an important brain region involved in cocaine addiction. Our results showed that chronic (13 d) but not acute (1 d) cocaine self-administration could significantly increase acetylation of H3 and H4 in rats' nucleus accumbens, while acetylation of H4 but not H3 dramatically increased after cocaine induced reinstatement of cocaine seeking behaviors in rats. These results suggested histone acetylation plays an important role in cocaine addiction.HDAC inhibitors inhibit the activity of HDAC and cause increased acetylation of histones. Sodium butyrate (NaBu), a potent HDAC inhibitor, has been proved to cause a more dramatic induction of H3 phosphoacetylation in striatum when administrated before cocaine. In this study, we investigated the effects of NaBu on additive behaviors. Our results showed that NaBu could significantly increase cocaine induced lever presses during cocaine self-administration and reinstatement of drug seeking behavior induced by cocaine (10 mg/kg, i.p.) priming or cue (light and tone) priming after extinction or cocaine withdrawal. Thus, our study shows that NaBu could alter cocaine related addictive behaviors and suggests a potential role of histone modification in explanation and treatment of cocaine addiction problems.