期刊
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
卷 36, 期 5, 页码 296-310出版社
CMA-CANADIAN MEDICAL ASSOC
DOI: 10.1503/jpn.100171
关键词
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资金
- Canadian Institutes of Health Research [MOP-74709]
- Natural Sciences and Engineering Research Council of Canada
- Fonds de la recherche en sante du Quebec
Changes in mesocorticolimbic dopamine (DA) neurons and their target cells can be induced throughout life and are important determinants of individual differences in susceptibility to psychopathology. The goal of my research is to gain insight into the nature of the cellular and molecular mechanism underlying the selective plasticity of mesocorticolimbic DA neurons. Here, I review work showing that the guidance cue netrin-1 is implicated in the organization, plasticity and function of mesocorticolimbic DA neurons in rodents. Developmental variations in netrin-1 receptor function result in selective reorganization of medial prefrontal DA circuitry during adolescence and in an adult phenotype protected against schizophrenia-like dopaminergic and behavioural abnormalities. Furthermore, in adulthood, expression of netrin-1 receptors is upregulated by repeated exposure to stimulant drugs of abuse in DA somatodendritic regions and is necessary for drug-induced behavioural plasticity. I propose that risk factors associated with DA-related adult psychiatric disorders alter netrin-1 function.
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