Atypical antipsychotic paliperidone prevents behavioral deficits in mice prenatally challenged with bacterial endotoxin lipopolysaccharide

作者：Kumar Umesh; Mohanty B****ata^*

来源：European Journal of Pharmacology, 2015, 747: 181-189.

DOI：10.1016/j.ejphar.2014.09.011

• Prenatal LPS challenge
• Behavioral deficits
• Antipsychotic drag
• Paliperidone

Studies on animal models provide enough evidences that old age appearance of psychosis on exposures to various insults during critical period of brain development could be prevented by antipsychotic drug treatment. Presently, gestational intervention of the atypical antipsychotic paliperidone (PAL) is done along with the exposure of bacterial endotoxin lipopolysaccharide/LPS hypothesizing that the drug would counteract and/or prevent the immune activation-induced behavioral deficits in mice. Effect of the PAL (0.05 mg/kg; GD 15-PND 28) in preventing reflex, sensorimotor and anxiety deficits in prenatally LPS-challenged (800 mu g/kg; GD 15 and GD 17) mice was assessed at three different life stages: neonatal (PND 4-PND 14), adolescence (PND 35) and at adulthood (PND 85). LPS-induced behavioral deficits were recognizable even at neonatal and adolescence stages, though more pronounced at adulthood. In only PAL-treated group few behavioral deficits though observed both at neonatal and adult stages but less prominent than LPS group were found. PAL co-treatment prevented the abnormalities in nest-seeking behavior in neonates, anxiety abnormalities at adolescence and adulthood but not the sensorimotor impairment. The drug might have maintained the stress homeostasis to counteract the behavioral abnormalities as LPS-induced hypercorticosteronemia was prevented on PAL co-treatment. In view of the in utero exposure, comparatively low drug dose was selected. Though efficacy has been predicted, the dose was not effective to prevent all psychopathological impairments. Considering the wider objectives, it was not possible to conduct multi dose study simultaneously. Our ongoing study with higher dose may predict the effective PAL dose in prevention of psychiatric illness.

• 出版日期2015-1-15