The gestational exposure in rats to clozapine promotes the spatial learning and memory and increases the phosphorylation of MAPK42 in the hippocampus of the adult offspring

The gestational exposure in rats to clozapine promotes the spatial learning and memory and increases the phosphorylation of MAPK42 in the hippocampus of the adult offspring

摘要

Objective The aim of this study was to examine the effect of gestational exposure to the antipsychotic clozapine in rats on the spatial learning and memory of adult offspring and to explore the underlying mechanism.Method During the middle period (G6-15) of gestation, pregnant female rats received intraperitoneal injection of clozapine (10 mg/kg) once a day.When growing into 8 week old, the males of the offspring were subjected to Morris water maze test to measure their spatial learning and memory.Their brain tissue was processed for Western blot analysis to assess levels of MAPK44/42 and phosphorylated MAPK44/42, and real time PCR to evaluate the expression of zif 268 gene Result The offspring with the history of prenatal exposure to clozapine showed better performance in the Morris water maze compared with the controls Western blot analysis showed a significant higher level of pMAPK 42 in the hippocampus of rats in the clozapine group, whereas no difference was found between the two groups in terms of the other indices.Conclusion These results suggest an important role of the MAPK42 phosphorylation in the promotion of the spatial learning and memory of adult offspring by clozapine given to pregnant female rats during the middle period of gestation