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Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice

Morcuende, S; Gadd, CA; Peters, M; Moss, A; Harris, EA; Sheasby, A; Fisher, AS; ... Hunt, SP; + view all (2003) Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice. EUR J NEUROSCI , 18 (7) 1828 - 1836. 10.1046/j.1460-9568.2003.02911.x.

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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.

Type: Article
Title: Increased neurogenesis and brain-derived neurotrophic factor in neurokinin-1 receptor gene knockout mice
DOI: 10.1046/j.1460-9568.2003.02911.x
Keywords: antidepressants, hippocampus, learning, substance P, SUBSTANCE-P RECEPTOR, ADULT-RAT HIPPOCAMPUS, DENTATE GYRUS, CELL-PROLIFERATION, ANTIDEPRESSANT TREATMENT, COGNITIVE FUNCTIONS, CONTEXTUAL FEAR, NK1 RECEPTOR, PHARMACOLOGICAL BLOCKADE, ENRICHED ENVIRONMENT
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: http://discovery.ucl.ac.uk/id/eprint/185754
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