Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.1.1.37 (
DNA methyltransferase
)
4,983
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An increasing number of reports have provided crucial evidence that epigenetic modifications, such as DNA methylation, may be involved in initiating and establishing psychostimulant-induced stable changes at the cellular level by coordinating the expression of gene networks, which then manifests as long-term behavioral changes. In this study, we evaluated the enzyme activity of DNA methyltransferases (DNMTs) after cocaine treatment and during withdrawal. Furthermore, we studied how genetic or pharmacological inhibition of DNMTs in mouse nucleus accumbens (NAc) affects the induction and expression of cocaine-induced behavioral sensitization. Our results showed that after silencing Dnmt3a in the NAc during the induction phase of cocaine-induced sensitization, overall
DNMT
activity decreases, correlating negatively with behavioral sensitization. Reduced Dnmt3a mRNA during this phase was the largest contributing factor for decreased
DNMT
activity.
Cocaine withdrawal
and a challenge dose increased
DNMT
activity in the NAc, which was associated with the expression of behavioral sensitization. Long-term selective Dnmt3a transcription silencing in the NAc did not alter
DNMT
activity or the expression of cocaine-induced behavioral sensitization. However, bilateral intra-NAc injection of a non-specific inhibitor of
DNMT
(RG108) during withdrawal from cocaine decreased
DNMT
activity in the NAc and had a small effect on the expression of cocaine-induced behavioral sensitization. Thus, cocaine treatment and withdrawal is associated with biphasic changes in
DNMT
activity in the NAc, and the expression of behavioral sensitization decreases with non-selective inhibition of
DNMT
but not with selective silencing of Dnmt3a.
...
PMID:The role of DNA methyltransferase activity in cocaine treatment and withdrawal in the nucleus accumbens of mice. 3073 91
