Increased GABABreceptor signaling in a rat model for schizophrenia.
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 GABABreceptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABABsignaling. Consistently, we find an increased expression of the GABAB1receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABABsignaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands.
Martijn M
MM
Selten
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Francisca
F
Meyer
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands.|Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Wei
W
Ba
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.|Department of Cognitive Neuroscience, Faculty of Psychology and Neurosciences, Maastricht University, Maastricht, the Netherlands.
Astrid
A
Vallès
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands.|Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Dorien A
DA
Maas
Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
Moritz
M
Negwer
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Vivian D
VD
Eijsink
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Ruben W M
RWM
van Vugt
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Josephus A
JA
van Hulten
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Nick H M
NHM
van Bakel
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Joey
J
Roosen
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Robert J
RJ
van der Linden
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands.
Dirk
D
Schubert
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands.
Michel M M
MMM
Verheij
Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands.|Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Nael Nadif
NN
Kasri
Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Gerard J M
GJM
Martens
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