Abstract
Treatment with an antagonist at the neurokinin-1 (NK-1) receptor may alleviate depression, however the brain region(s) in which the NK-1 receptor antagonist exerts its therapeutic effect is unknown. [125I]BH-Substance P was used to measure NK-1 receptors postmortem in cytoarchitectonically defined areas of rostral orbitofrontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-1 receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-1 receptor antagonists, may thus involve NK-1 receptors in prefrontal cortex.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Age Factors
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Aged
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Aged, 80 and over
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Binding Sites / physiology
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Binding, Competitive / physiology
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Brain Chemistry / drug effects
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Brain Chemistry / physiology*
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Depressive Disorder, Major / drug therapy
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Depressive Disorder, Major / metabolism*
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Depressive Disorder, Major / physiopathology
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Down-Regulation / physiology*
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Female
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Humans
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Male
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Middle Aged
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Neurokinin-1 Receptor Antagonists
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Neurons / drug effects
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Neurons / metabolism*
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / metabolism*
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Prefrontal Cortex / physiopathology
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Radioligand Assay
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Receptors, Neurokinin-1 / metabolism*
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Substance P / antagonists & inhibitors
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Substance P / metabolism*
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Suicide
Substances
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Neurokinin-1 Receptor Antagonists
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Receptors, Neurokinin-1
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Substance P