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- Title
Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice.
- Authors
Morcuende, Sara; Gadd, Christopher A.; Peters, Marco; Moss, Andrew; Harris, Elizabeth A.; Sheasby, Anne; Fisher, Amy S.; De Felipe, Carmen; Mantyh, Patrick W.; Rupniak, Nadia M. J.; Giese, K. Peter; Hunt, Stephen P.
- Abstract
It has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain-derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long-term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin-1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin-1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin-1 receptor knockout mice. Neurogenesis can be increased in wild-type but not neurokinin-1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain-derived neurotrophic factor are also two-fold higher in neurokinin-1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus-dependent learning and memory but found no clear enhancement in neurokinin-1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain-derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain-derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy.
- Subjects
TACHYKININS; DEVELOPMENTAL neurobiology
- Publication
European Journal of Neuroscience, 2003, Vol 18, Issue 7, p1828
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1046/j.1460-9568.2003.02911.x