Early enriched environment prevents cognitive impairment in an animal model of schizophrenia induced by MK-801: Role of hippocampal BDNF

Abstract

Early life experience has long-lasting effects on brain and behaviour. This study aims to investigate the long-term effects of enriched environment (EE), which was imposed during the animals' development, on their recognition memory as well as hippocampal levels of brain-derived neurotrophic factor (BDNF), in an animal model of schizophrenia induced by chronic postnatal administration of MK-801. Forty male and female rat pups were separated in four distinct groups for each sex (n = 10). The rats were injected with MK-801 (1 mg/kg) or saline (1 cc/kg) on their postnatal days (P) 6-10. MK-801 and Control rats were maintained in standard or enriched cages (containing toys, tunnels, running wheels, and climbing frame), from their birth up to the time of behavioral experiments at P60. Neonatal challenge with MK-801 significantly impaired novel object recognition (NOR) in both male and female animals. EE exposure reversed the recognition memory only in male rats. MK-801 resulted in decreased levels of BDNF in the hippocampus, and EE exposure restored the decreased level. Our results provide evidence that BDNF plays an important role in pathophysiology of schizophrenia in the present animal model, and is a possible mechanism through which early EE can enhance the cognitive functions.

Keywords: Brain-derived neurotrophic factor; Enriched environment; MK-801; Novel object recognition; Schizophrenia.