期刊
SCHIZOPHRENIA RESEARCH
卷 215, 期 -, 页码 485-492出版社
ELSEVIER
DOI: 10.1016/j.schres.2017.07.016
关键词
Reelin; Psychosis; Behavioural despair; Dopamine; Memory
类别
资金
- Australian Postgraduate Award
- National Health and Medical Research Council of Australia
- School of Psychology and Public Health at La Trobe University, Melbourne, Australia
Rationale: Psychotic disorders, such as schizophrenia, as well as some mood disorders, such as bipolar disorder, have been suggested to share common biological risk factors. One such factor is reelin, a large extracellular matrix glycoprotein that regulates neuronal migration during development as well as numerous activity-dependent processes in the adult brain. The current study sought to evaluate whether a history of stress exposure interacts with endogenous reelin levels to modify behavioural endophenotypes of relevance to psychotic and mood disorders. Methods: Heterozygous Reeler Mice (HRM) and wildtype (WT) controls were treated with 50 mg/L of corticosterone (CORT) in their drinking water from 6 to 9 weeks of age, before undergoing behavioural testing in adulthood. We assessed methamphetamine-induced locomotor hyperactivity, prepulse inhibition (PPI) of acoustic startle, short-term spatial memory in the Y-maze, and depression-like behaviour in the Forced-Swim Test (FST). Results: HRM genotype or CORT treatment did not affect methamphetamine-induced locomotor hyperactivity, a model of psychosis-like behaviour. At baseline, HRM showed decreased PPI at the commonly used 100 msec interstimulus interval (ISI), but not at the 30 msec ISI or following challenge with apomorphine. A history of CORT exposure potentiated immobility in the FST amongst HRM, but not WT mice. In the Y-maze. chronic CORT treatment decreased novel arm preference amongst HRM, reflecting reduced short-term spatial memory. Conclusion: These data confirm a significant role of endogenous reelin levels on stress-related behaviour, supporting a possible role in both bipolar disorder and schizophrenia. However, an interaction of reelin deficiency with dopaminergic regulation of psychosis-like behaviour remains unclear. (C) 2017 Elsevier B.V. All rights reserved.
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