Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice.

ABSTRACT:

Background

Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility.

Methods

In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL.

Results

Our results show that the motor side

SUBMITTER: Montalvo-Ortiz JL 

PROVIDER: S-EPMC5538925 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature