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Early antipsychotic treatment in juvenile rats elicits long-term alterations to the adult serotonin receptors

Authors De Santis M, Huang XF, Deng C

Received 1 December 2017

Accepted for publication 9 March 2018

Published 14 June 2018 Volume 2018:14 Pages 1569—1583

DOI https://doi.org/10.2147/NDT.S158545

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Professor Wai Kwong Tang


Michael De Santis,1,2 Xu-Feng Huang,2 Chao Deng1,2

1Antipsychotic Research Laboratory, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia; 2School of Medicine, University of Wollongong, Wollongong, NSW, Australia

Background: Antipsychotic drug (APD) prescription/use in children has increased significantly worldwide, despite limited insight into potential long-term effects of treatment on adult brain functioning. While initial long-term studies have uncovered alterations to behaviors following early APD treatment, further investigations into potential changes to receptor density levels of related neurotransmitter (NT) systems are required.
Methods: The current investigation utilized an animal model for early APD treatment with aripiprazole, olanzapine, and risperidone in male and female juvenile rats to investigate potential long-term changes to the adult serotonin (5-HT) NT system. Levels of 5-HT1A, 5-HT2A, and 5-HT2C receptors were measured in the prefrontal cortex (PFC), caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus via Western Blot and receptor autoradiography.
Results: In the male cohort, long-term changes to 5-HT2A and 5-HT2C receptors were found mostly across hippocampal and cortical brain regions following early aripiprazole and olanzapine treatment, while early risperidone treatment changed 5-HT1A receptor levels in the NAc and PFC. Lesser effects were uncovered in the female cohort with aripiprazole, olanzapine and risperidone to alter 5-HT1A and 5-HT2A receptors in NAc and hippocampal brain regions, respectively.
Conclusion: The results of this study suggest that early treatment of various APDs in juvenile rats may cause gender and brain regional specific changes in 5-HT2A and 5-HT2C receptors in the adult brain.

Keywords:
antipsychotic drug, serotonin, risperidone, olanzapine, aripiprazole, development, juvenile

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