Increased GABA B receptor signaling in a rat model for schizophrenia.

Autor: Selten MM; Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands., Meyer F; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., Ba W; 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., Vallès A; 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., Maas DA; 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., Negwer M; Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands., Eijsink VD; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., van Vugt RWM; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., van Hulten JA; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., van Bakel NHM; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., Roosen J; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., van der Linden RJ; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands., Schubert D; Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands., Verheij MMM; Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition, and Behaviour, Nijmegen, the Netherlands., Kasri NN; 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., Martens GJM; Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Nijmegen, the Netherlands.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2016 Sep 30; Vol. 6, pp. 34240. Date of Electronic Publication: 2016 Sep 30.
DOI: 10.1038/srep34240
Abstrakt: 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 B receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABA B signaling. Consistently, we find an increased expression of the GABA B1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABA B signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.
Databáze: MEDLINE