295. EFFECTS OF ANTIPSYCHOTICS AND PRENATAL POLY I:C EXPOSURE ON GSK3β-MEDIATED SIGNALING AND NMDA/GABA RECEPTORS IN THE DORSAL RAPHE NUCLEUS OF RATS

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Abstract Background The dorsal raphe nucleus (DRN) in the midbrain is the original of the serotoninergic (5-HT) neurotransmission pathways. The 5-HT, dopamine D2, γ-Aminobutyric acid (GABA), and glutamatergic N-methyl-D-aspartate (NMDA) receptors, as well as cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway and G protein-independent protein kinase B (PKB/Akt)-glycogen synthase kinase 3 beta (GSK3β) signaling pathways, are involved in the pathophysiology of schizophrenia and modulated by antipsychotics. Aims & Objectives To investigate the pathological changes of these biomarkers in the DRN and antipsychotics modulations on relevant signaling pathways in a schizophrenia rat model. Method Using a maternal immune activation (MIA) rat model induced by prenatal polyriboinosinic-polyribocytidylicacid (Poly I:C) exposure, this study explored the effect of antipsychotic (risperitoneand olanzapine) treatment on GABAA, and NMDA receptors, as well as PKA, AKT-GSK3β, cAMP-responsive element-binding protein 1 (CREB1), Disheveled (Dvl)-β-catenin signaling in the DRN. Results Our results revealed that prenatal Poly I:C exposure increased mRNA expression of GABAA receptor β3 subunit, glutamic acid decarboxylase1 (GAD1), NMDA receptor Grin2a/2b subunits, AKT1/3 and GSK3β in the DRN. Antipsychotic treatment significantly increased the mRNA expression of PKA, CREB1, β-catenin, GSK3β, and Grin2d subunits in the DRN of rats with prenatal Poly I:C exposure. Prenatal Poly I:C exposure led to decreased expression of glutamic acid decarboxylase2 (GAD2), while antipsychotics partially reversed the decreased GAD2 expression. This study suggests that Poly I:C-elicited maternal immune activation and antipsychotics differentially modulate NMDA and GABAAreceptors, as well as AKT-GSK3β, PKA-CREB1, Dvl-β-catenin signaling in the DRN of rats. Discussion & Conclusions Prenatal Poly I:C exposure mainly influenced AKT-GSK3β singling pathway, while antipsychotics treatment could modulate AKT-GSK3β, PKA-CREB1 and Dvl-GSK3β-β-catenin signaling pathways in the DRN.

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