DNA Methyltransferase Inhibitor Successfully Treats Obsessive-Compulsive Disorder in Various Mouse Models

Author Info

German Todorov David Ashurov Catarina Cunha

Corresponding Author

Catarina Cunha
Emotional Brain Institute, Nathan Kline Institute, Orangeburg, New York, USA

A B S T R A C T

Mental health disorders are manifested in families yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviours, which upon repetition may become habitual, maladaptive, and resistant to extinction as observed in obsessive-compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long-term OCD-like behaviour in mice associated with circuitry changes and gene methylation-mediated decrease in protein phosphatase 1 (PP1). Treatment of OCD-like grooming behaviour in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), leads to marked symptom improvement lasting for at least one week as well as a complete reversal of abnormal changes in the circuitry and PP1 activity.

Article Info

Article Type

Research Article

Publication history

Received: Fri 26, Feb 2021
Accepted: Thu 18, Mar 2021
Published: Wed 31, Mar 2021

Copyright

© 2023 Catarina Cunha. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.NNB.2021.01.02