Cocaine-induced epigenetic DNA modification in mouse addiction-specific and non-specific tissues.

Cocaine-induced epigenetic DNA modification in mouse addiction-specific and non-specific tissues. Neuropharmacology. 2018 Jun 28;: Authors: Anier K, Urb M, Kipper K, Herodes K, Timmusk T, Zharkovsky A, Kalda A Abstract Cocaine-related DNA methylation studies have primarily focused on the specific brain regions associated with drug addiction (e.g., the nucleus accumbens, NAc). To date, no studies have focused on the complex role of both DNA methylation and demethylation in the mechanisms of psychostimulant-induced addiction in the brain and peripheral tissues. Therefore, in this study, we evaluated cocaine treatment and withdrawal (animals were withdrawn from seven days of repeated injections of cocaine that caused behavioral sensitization) effects on epigenetic DNA modifiers (i.e., DNA methyltransferases, [DNMTs] and ten-eleven translocation enzymes [TETs]) in an addiction-specific brain region (NAc), a structure outside the mesolimbic dopaminergic system (cerebellum, Cer), and in peripheral blood cells (PBCs). Using a mouse behavioral sensitization model, we demonstrated that acute cocaine (AC; 0.5 h) treatment significantly decreased Dnmt1, Dnmt3a, Tet1, and Tet2 mRNA levels in the NAc and PBC, whereas at 24 h after AC treatment, Dnmt mRNA expression and enzyme activity levels were significantly increased. Acute procaine treatment caused the opposite effect on the Dnmt3a mRNA level in PBCs; this outcome suggests that the inhibi...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research