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Long-term effects of cariprazine exposure on dopamine receptor subtypes

Published online by Cambridge University Press:  08 November 2013

Yong Kee Choi ,
Nika Adham ,
Béla Kiss ,
István Gyertyán  and
Frank I. Tarazi
Yong Kee Choi
Affiliation:
Department of Psychiatry & Neuroscience, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, USA
Nika Adham
Affiliation:
Department of Pharmacology, Forest Research Institute, Jersey City, New Jersey, USA
Béla Kiss
Affiliation:
Department of Pharmacological and Safety Research, Gedeon Richter Plc, Budapest, Hungary
István Gyertyán
Affiliation:
Department of Behavioral Pharmacology, Division of Pharmacology and Drug Safety Research, Gedeon Richter Plc, Budapest, Hungary
Frank I. Tarazi*
Affiliation:
Department of Psychiatry & Neuroscience, Harvard Medical School and McLean Hospital, Belmont, Massachusetts, USA
*
*Address for correspondence: Frank I. Tarazi, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA. (Email: ftarazi@hms.harvard.edu)
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Abstract

Introduction

All clinically effective antipsychotics are known to act on the dopaminergic system, and previous studies have demonstrated that repeated treatment with antipsychotics produced region-specific changes in dopamine receptor levels. Cariprazine is a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. We examined the effects of chronic cariprazine administration on dopamine receptor levels.

Methods

Rats were administered either vehicle or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Dopamine receptor levels were quantitated using autoradiographic assays on brain tissue sections from the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), caudate putamen (CPu), hippocampus (HIPP), olfactory tubercle (OT), and islands of Calleja (ICj).

Results

Chronic treatment with cariprazine did not alter D1 receptor levels in any brain region tested. Cariprazine increased D2 receptor levels in mPFC (27%–43%), NAc (40%–45%), medial (41%–53%) and lateral (52%–63%) CPu, and HIPP (38%). Cariprazine dose-dependently upregulated D3 receptor levels in ICj (32%–57%), OT (27%–67%), and NAc shell (31%–48%). Repeated cariprazine treatment increased D4 receptor in NAc (53%–82%), medial (54%–98%) and lateral (58%–74%) CPu, and HIPP (38%–98%).

Conclusion

Similar to other antipsychotics, cariprazine upregulated D2 and D4 receptor levels in various brain regions. Cariprazine was unique among antipsychotics in increasing D3 receptor levels, which may support its unique psychopharmacologic properties.

Keywords

Antipsychotic drugsautoradiographycariprazinedopamine receptorsschizophrenia
Type
Original Research
Information
CNS Spectrums , Volume 19 , Issue 3 , June 2014 , pp. 268 - 277
Copyright
Copyright © Cambridge University Press 2013 

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Footnotes

This study was funded by Forest Laboratories, Inc. and Gedeon Richter Plc. The authors would like to thank Vojislav Pejovic, PhD, and Adam Ruth, PhD, of Prescott Medical Communications Group for their technical writing, editing, and research support.

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