Effects of gestational haloperidol exposure on mRNA expressions related to glutamine and GABA receptors in offspring

Objectives: The aim of the present study was to investigate the effects of intraperitoneal haloperidol (HAL) injection to pregnant mice on glutamine and GABA receptors in the brain of offspring mice. Method: Eight-week-old pregnant mice were treated with either intraperitoneal HAL or normal saline injection, and their offspring were defined as F1 mice. In addition, eight-week-old male mice were used as acute mice that were intraperitoneally injected with HAL or normal saline for 20 days. F1 and acute mice were sacrificed by decapitation, and their hippocampi, frontal lobes, and temporal lobes were collected. RNA was isolated, and mRNA expression levels were measured by RT-qPCR. Western blotting was performed using the frontal lobes of F1 mice. Results: In the hippocampi of F1 mice, Grik3 (p = 0.023) and Gabra3 (p = 0.004) mRNA expression levels were significantly higher in the HAL group than in the control group, whereas Gria2 (p < 0.001) and Grin2a (p < 0.001) mRNA expression levels were significantly lower in the HAL group than in the control group. Gria2 (p = 0.015), Grik3 (p = 0.037), and Grin2a (p = 0.012) mRNA expression levels were significantly lower in the HAL group than in the control group in the frontal lobes of F1 mice. In the hippocampi of acute mice, Grik3 (p = 0.049) and Gabra3 (p = 0.007) mRNA expressions were significantly increased in the HAL group. Conclusions: The present results may explain the effects of fetal exposure to antipsychotics on neurodevelopmental modifications and teratogenicity.