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Low prefrontal PSA-NCAM confers risk for alcoholism-related behavior

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.

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Figure 1: Individual differences in PIT predict ethanol extinction and reinstatement.
Figure 2: vmPFC PSA-NCAM regulates extinction of ethanol seeking.

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Acknowledgements

This research was supported by National Institutes of Health grants P50 AA012870 (J.R.T.), R01 DA011717 (J.R.T.), F31 AA020135 (J.M.B.) and K01 DA031745 (M.M.T.), and the Connecticut Department of Mental Health and Addiction Services. The PSA-NCAM antibody developed by T.M. Jessell, J. Dodd and S. Brenner-Morton (Center for Neurobiology and Behavior, Columbia University) was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by the University of Iowa.

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J.M.B., M.M.T. and J.R.T. designed the study and wrote the manuscript. J.M.B. performed the experiments and analyzed the data.

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Correspondence to Jane R Taylor.

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The authors declare no competing financial interests.

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Barker, J., Torregrossa, M. & Taylor, J. Low prefrontal PSA-NCAM confers risk for alcoholism-related behavior. Nat Neurosci 15, 1356–1358 (2012). https://doi.org/10.1038/nn.3194

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