Administration of ketamine to neonatal SD rats causes abnormal prefrontal cortex development and mood disorders in adult

Abstract

Objective To investigate the effect of ketamine administration to neonatal SD rats on prefrontal cortex development and emotional state in adult.Methods Forty postnatal day 7 (P7) SD rats were randomly assigned to receive intraperitoneal injection of 50 mg/kg ketamine (K group) or 0.25 ml saline (NS group),once every 30 min for totally 4 times.The expression of cysteinyl aspartate-specific protease-3 (Caspase-3) in the prefrontal cortex was detected by Western blotting at 6 h after the last injection,and the remaining pups were allowed to grow up with their mothers until P30.Behavioral tests were done to evaluate cognitive function and mood state on P30-P33.After behavioral tests,rats were sacrificed for Nissl staining to study the cytoarchitecture development of prefrontal cortex.Results P7 rats exposed to ket-amine caused up-regulated expression of Caspase-3 in the prefrontal cortex (n =5,P ＜ 0.05).At P30,as compared with control group,the center area of the environment [NS group:(25.9 ± 2.2) s,K group:(16.5±2.0) s,n=15,P＜0.01],sucrose intake [NS group:(77.0±2.5)％,K group:(60.0±4.3) ％,n =15,P ＜ 0.01],and the cell density in the prefrontal cortex [NS group:(1 367 ± 79) cells/mm2,K group:(1 105 ± 73) cells/mm2,n =6,P ＜ 0.05] were significandy reuced in K group.Conclusion Administration of ketamine to neonatal SD rats causes depression-and anxiety-like behaviors in adult,which may be associated with cell apoptosis by up-regulating the Caspase-3 expresion and neuronal loss in the prefrontal cortex. Key words: Ketamine; Prefrontal cortex; Mood disorder; Depression; Anxiety