Abstract
The factors underlying vulnerability to alcoholism are largely unknown. We identified in rodents an innate endophenotype predicting individual risk for alcohol-related behaviors that was associated with decreased expression of the neuroplasticity-related polysialylated neural cell adhesion molecule (PSA-NCAM). Depletion of PSA-NCAM in the ventromedial prefrontal cortex was sufficient to render mice unable to extinguish alcohol seeking, indicating a causal role of naturally occurring variation. These data suggest a mechanism of aberrant prefrontal neuroplasticity that underlies enhanced propensity for inflexible addiction-related behavior.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alcoholism / metabolism*
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Alcoholism / psychology*
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Animals
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Behavior, Addictive / metabolism
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Behavior, Addictive / physiopathology*
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Cues
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Disease Models, Animal
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Ethanol / administration & dosage
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Ethanol / pharmacology
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Extinction, Psychological / drug effects
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Extinction, Psychological / physiology
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Glycoside Hydrolases / pharmacology
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Male
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Mice
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Mice, Inbred ICR
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Neural Cell Adhesion Molecule L1 / metabolism
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Neural Cell Adhesion Molecule L1 / physiology*
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Neural Cell Adhesion Molecules / metabolism
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Neuronal Plasticity / physiology
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / metabolism
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Prefrontal Cortex / physiology*
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Self Administration
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Sialic Acids / metabolism
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Sialic Acids / physiology*
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Transfer, Psychology / drug effects
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Transfer, Psychology / physiology
Substances
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Neural Cell Adhesion Molecule L1
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Neural Cell Adhesion Molecules
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Sialic Acids
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polysialyl neural cell adhesion molecule
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Ethanol
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Glycoside Hydrolases
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endo-alpha-sialidase