Chronic Clozapine Treatment Impairs Functional Activation of Metabotropic Glutamate Receptor 2 via an HDAC2-depedent Mechanism

Author

Travis M. CuddyFollow

DOI

https://doi.org/10.25772/ZD8V-9870

Defense Date

2018

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Javier González-Maeso

Second Advisor

Laura Sim-Selley

Third Advisor

Dana Selley

Fourth Advisor

Roland Pittman

Abstract

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT_2A-dependent upregulation of histone deacetylase 2 (HDAC2), which in turn leads to downregulation of metabotropic glutamate receptor 2 (mGluR2), a G protein-coupled receptor with an important role in synaptic plasticity. The present study aims to characterize the extent to which this downregulation leads to specific functional outcomes, and in doing so, may help identify new targets for more effective treatment of schizophrenia.

Rights

© Travis M. Cuddy

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-10-2018