Increased GABA Receptor Signaling in a Rat Model for Schizophrenia

Overview

Journal Sci Rep

Specialty Science

Date 2016 Oct 1

PMID 27687783

Citations 8

Authors

Martijn M Selten

Francisca Meyer

Wei Ba

Astrid Valles

Dorien A Maas

Moritz Negwer

Vivian D Eijsink

Ruben W M van Vugt

Josephus A van Hulten

Nick H M van Bakel

Joey Roosen

Robert J van der Linden

Dirk Schubert

Michel M M Verheij

Nael Nadif Kasri

Gerard J M Martens

Affiliations

Soon will be listed here.

Abstract

Schizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20-22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABA receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABA signaling. Consistently, we find an increased expression of the GABA receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABA signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.

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