NDLI: Aripiprazole Increases the PKA Signalling and Expression of the GABA$_{A}$ Receptor and CREB1 in the Nucleus Accumbens of Rats

Content Provider	Springer Nature Link
Author	Pan, Bo Lian, Jiamei Huang, Xu Feng Deng, Chao
Copyright Year	2016
Abstract	The GABA$_{A}$ receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D$_{2}$-like receptors, but not the GABA$_{A}$ receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D$_{2}$-mediated PKA signalling and its downstream GABA$_{A}$ receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-Cα and p-PKA in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) were detected by Western blots. The mRNA levels of Gabrb1, Gabrb2, Gabrb3 and Creb1, and their protein expression were measured by qRT-PCR and Western blots, respectively. Aripiprazole elevated the levels of p-PKA and the ratio of p-PKA/PKA in the NAc, but not the PFC and CPu. Correlated with this elevated PKA signalling, aripiprazole elevated the mRNA and protein expression of the GABA$_{A}$ (β-1) receptor and CREB1 in the NAc. While haloperidol elevated the levels of p-PKA and the ratio of p-PKA/PKA in both NAc and CPu, it only tended to increase the expression of the GABA$_{A}$ (β-1) receptor and CREB1 in the NAc, but not the CPu. Bifeprunox had no effects on PKA signalling in these brain regions. These results suggest that aripiprazole has selective effects on upregulating the GABA$_{A}$ (β-1) receptor and CREB1 in the NAc, probably via activating PKA signalling.
Starting Page	36
Ending Page	47
Page Count	12
File Format	PDF
ISSN	08958696
Journal	Journal of Molecular Neuroscience
Volume Number	59
Issue Number	1
e-ISSN	15591166
Language	English
Publisher	Springer US
Publisher Date	2016-02-19
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Antipsychotics Aripiprazole Bifeprunox PKA CREB1 Haloperidol GABA$_{A}$ receptors Neurosciences Neurochemistry Cell Biology Proteomics Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Cellular and Molecular Neuroscience

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