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FC29-03 - Effects of chronic oral treatment with aripiprazole on expression of nmda receptor subunits and binding sites in rat brain

Published online by Cambridge University Press:  16 April 2020

M. Zink ,
N. Segnitz ,
T. Ferbert ,
A. Schmitt ,
P. Gass  and
P.J. Gebicke-Härter
M. Zink
Affiliation:
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
N. Segnitz
Affiliation:
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
T. Ferbert
Affiliation:
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
A. Schmitt
Affiliation:
Department of Psychiatry, University of Goettingen, Goettingen, Germany
P. Gass
Affiliation:
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany
P.J. Gebicke-Härter
Affiliation:
Department of Psychopharmacology, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

Abstract

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Introduction

The glutamatergic theory of schizophrenia proposes a dysfunction of ionotropic N-Methyl-D-aspartate (NMDA)-receptors (NR). Several therapeutic strategies address NR function and effects of antipsychotic agents on NR expression have been described.

Objectives

The partial dopaminergic and serotonergic agonist aripiprazole (APZ) was able to counteract behavioural effects of NR antagonists, but effects of APZ on NR expression have not been investigated.

Aims

To evaluate effects of APZ on NR mRNA and protein expression

Methods

We treated Sprague-Dawley rats for 4 weeks or 4 months with APZ in daily oral doses of 10 and 40 mg per kg body weight. Expression of the NR subunits NR1, NR2A, NR2B, NR2C and NR2D was assessed by semiquantitative radioactive in situ-hybridization, and in parallel receptor binding using 3H-MK-801 receptor autoradiography.

Results

Increased expression levels of NR1 (4 weeks), NR2A (4 weeks), NR2C (4 weeks and 4 months) and NR2D (4 months) were observed in several hippocampal and cortical brain regions. The parallel reduced expression of NR2B mRNAs (4 months) resulted in a relative increase of the NR2A/NR2B ratio. Marked differences between specific brain regions, the doses and time points of assessment became obvious. On the receptor level, increased MK-801-binding was found after 4 weeks in the 40 mg-group and after 4 months in the 10 mg-group.

Conclusions

The effects of APZ converge in enhanced NMDA-receptor expression and a shift of subunit-composition towards adult-type receptors. Our results confirm regulatory connections between dopaminergic, serotonergic and glutamatergic neurotransmission with relevance for cognitive and negative symptoms of schizophrenia.

Type
Research Article
Information
European Psychiatry , Volume 26 , Issue S2: Abstracts of the 19th European Congress of Psychiatry , March 2011 , pp. 1979
Copyright
Copyright © European Psychiatric Association 2011
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