Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits
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 a...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-01-01
|
| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00260/full |
| _version_ | 1811274973782736896 |
|---|---|
| author | Xiao Liu Xiao Liu Xiao Liu Jitao Li Chunmei Guo Hongli Wang Yaxin Sun Han Wang Yun-Ai Su Keqing Li Keqing Li Tianmei Si |
| author_facet | Xiao Liu Xiao Liu Xiao Liu Jitao Li Chunmei Guo Hongli Wang Yaxin Sun Han Wang Yun-Ai Su Keqing Li Keqing Li Tianmei Si |
| author_sort | Xiao Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T23:29:52Z |
| format | Article |
| id | doaj.art-cb8a0549c5fb4f5587b1ecaefce87197 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-12T23:29:52Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-cb8a0549c5fb4f5587b1ecaefce871972022-12-22T03:12:19ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532018-01-011110.3389/fnbeh.2017.00260326328Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor SubunitsXiao Liu0Xiao Liu1Xiao Liu2Jitao Li3Chunmei Guo4Hongli Wang5Yaxin Sun6Han Wang7Yun-Ai Su8Keqing Li9Keqing Li10Tianmei Si11Institute of Psychology, North China University of Science and Technology, Tangshan, ChinaThe Sixth People’s Hospital of Hebei Province, Baoding, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaInstitute of Psychology, North China University of Science and Technology, Tangshan, ChinaThe Sixth People’s Hospital of Hebei Province, Baoding, ChinaNational 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, ChinaCognitive 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.http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00260/fullMK-801olanzapinecognitionschizophreniaNMDA receptorprefrontal cortex |
| spellingShingle | Xiao Liu Xiao Liu Xiao Liu Jitao Li Chunmei Guo Hongli Wang Yaxin Sun Han Wang Yun-Ai Su Keqing Li Keqing Li Tianmei Si Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits Frontiers in Behavioral Neuroscience MK-801 olanzapine cognition schizophrenia NMDA receptor prefrontal cortex |
| title | Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits |
| title_full | Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits |
| title_fullStr | Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits |
| title_full_unstemmed | Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits |
| title_short | Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits |
| title_sort | olanzapine reverses mk 801 induced cognitive deficits and region specific alterations of nmda receptor subunits |
| topic | MK-801 olanzapine cognition schizophrenia NMDA receptor prefrontal cortex |
| url | http://journal.frontiersin.org/article/10.3389/fnbeh.2017.00260/full |
| work_keys_str_mv | AT xiaoliu olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT xiaoliu olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT xiaoliu olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT jitaoli olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT chunmeiguo olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT hongliwang olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT yaxinsun olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT hanwang olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT yunaisu olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT keqingli olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT keqingli olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits AT tianmeisi olanzapinereversesmk801inducedcognitivedeficitsandregionspecificalterationsofnmdareceptorsubunits |