4.7 Article

Effects of Risperidone and Prenatal Poly I:C Exposure on GABAA Receptors and AKT-GSK3β Pathway in the Ventral Tegmental Area of Female Juvenile Rats

Journal

BIOMOLECULES
Volume 12, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/biom12050732

Keywords

maternal immune activation; risperidone; ventral tegmental area; GSK3 beta; GABA(A) receptor

Funding

  1. Australian National Health and Medical Research Council (NHMRC) [APP 1104184]
  2. NHMRC Early Career Fellowship Award [APP1125937]
  3. Young Core Teacher Fund of Fujian Medical University [JGG201308]

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This study investigated the effects of adolescent risperidone treatment on GABA(A) receptors and AKT/GSK3 beta in the ventral tegmental area. The results showed that risperidone partially reversed the decreased expression of GAD2 and had differential effects on GABAergic neurotransmission and AKT-GSK3 beta signaling.
The ventral tegmental area (VTA) in the ventral midbrain is the origin of the dopaminergic neurotransmission pathways. Although GABA(A) receptors and AKT-GSK3 beta signaling are involved in the pathophysiology of mental disorders and are modulated by antipsychotics, an unmet task is to reveal the pathological changes in these biomarkers and antipsychotic modulations in the VTA. Using a juvenile polyriboinosinic-polyribocytidylic acid (Poly I:C) psychiatric rat model, this study investigated the effects of adolescent risperidone treatment on GABA(A) receptors and AKT/GSK3 beta in the VTA. Pregnant female Sprague-Dawley rats were administered Poly I:C (5mg/kg; i.p) or saline at gestational day 15. Juvenile female offspring received risperidone (0.9 mg/kg, twice per day) or a vehicle from postnatal day 35 for 25 days. Poly I:C offspring had significantly decreased mRNA expression of GABA(A) receptor beta 3 subunits and glutamic acid decarboxylase (GAD2) in the VTA, while risperidone partially reversed the decreased GAD2 expression. Prenatal Poly I:C exposure led to increased expression of AKT2 and GSK3 beta. Risperidone decreased GABA(A) receptor beta 2/3, but increased AKT2 mRNA expression in the VTA of healthy rats. This study suggests that Poly I:C-elicited maternal immune activation and risperidone differentially modulate GABAergic neurotransmission and AKT-GSK3 beta signaling in the VTA of adolescent rats.

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