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Neuropsychopharmacology. 2018 Jun;43(7):1539-1547. doi: 10.1038/s41386-018-0012-1. Epub 2018 Feb 7.

mTORC2 in the dorsomedial striatum of mice contributes to alcohol-dependent F-Actin polymerization, structural modifications, and consumption.

Author information

1
Department of Neurology, University of California, San Francisco, San Francisco, CA, 94143, USA.
2
N.M. Brains On-line LLC, South San Francisco, CA, USA.
3
S.L. GIGA-Neurosciences, University of Liège, Liège, Belgium.
4
Department of Neurology, University of California, San Francisco, San Francisco, CA, 94143, USA. dorit.ron@ucsf.edu.

Abstract

Actin is highly enriched at dendritic spines, and actin remodeling plays an essential role in structural plasticity. The mammalian target of rapamycin complex 2 (mTORC2) is a regulator of actin polymerization. Here, we report that alcohol consumption increases F-actin content in the dorsomedial striatum (DMS) of mice, thereby altering dendritic spine morphology in a mechanism that requires mTORC2. Specifically, we found that excessive alcohol consumption increases mTORC2 activity in the DMS, and that knockdown of Rictor, an essential component of mTORC2 signaling, reduces actin polymerization, and attenuates the alcohol-dependent alterations in spine head size and the number of mushroom spines. Finally, we show that knockdown of Rictor in the DMS reduces alcohol consumption, whereas intra-DMS infusion of the mTORC2 activator, A-443654, increases alcohol intake. Together, these results suggest that mTORC2 in the DMS facilitates the formation of F-actin, which in turn induces changes in spine structure to promote and/or maintain excessive alcohol intake.

PMID:
29497165
PMCID:
PMC5983552
DOI:
10.1038/s41386-018-0012-1
[Indexed for MEDLINE]
Free PMC Article

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