Psychopharmacology (2017) 234:2385–2398 DOI 10.1007/s00213-017-4629-2 ORIGINAL INVESTIGATION Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice 1 2 1 3 Janitza L. Montalvo-Ortiz & Daniel W. Fisher & Guadalupe Rodríguez & Deyu Fang & 1 1 John G. Csernansky & Hongxin Dong Received: 1 January 2017 /Accepted: 4 April 2017 /Published online: 18 April 2017 Springer-Verlag Berlin Heidelberg 2017 Abstract specific lysine residues of H3 and H4 within the Drd2 pro- Background Older patients can be especially susceptible to moter in the striatum of aged mice. HDAC inhibitors, partic- antipsychotic-induced side effects, and the pharmacodynamic ularly VPA, restored striatal D2R protein levels and function- mechanism underlying this phenomenon remains unclear. We ality and reversed age- and drug-related histone modifications hypothesized that age-related epigenetic alterations lead to at the Drd2 promoter. decreased expression and functionality of the dopamine D2 Conclusions These results suggest that epigenetic changes at receptor (D2R), contributing to this susceptibility. the striatal Drd2 promoter drive age-related increases in anti- Methods In this study, we treated young (2–3 months old) and psychotic side effect susceptibility, and HDAC inhibitors may aged (22–24 months old) C57BL/6 mice with the D2R antag- be an effective adjunct treatment
Psychopharmacology – Springer Journals
Published: Apr 18, 2017
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