Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

Frontiers in Behavioral Neuroscience

Xiao Liu²  Hongli Wang²  Yun-Ai Su²  Chunmei Guo²  Yaxin Sun²  Jitao Li²  Han Wang²  Tianmei Si²  Keqing Li³ 

[1] Institute of Psychology, North China University of Science and Technology, Tangshan, China;National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital/Institute of Mental Health) and The Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China;The Sixth People’s Hospital of Hebei Province, Baoding, China;

关键词: MK-801;    olanzapine;    cognition;    schizophrenia;    NMDA receptor;    prefrontal cortex;   

DOI  :  10.3389/fnbeh.2017.00260

来源: DOAJ

【 摘 要 】

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine.

【 授权许可】

Unknown