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Nat Commun. 2013;4:1955. doi: 10.1038/ncomms2955.

Hypothalamic proteoglycan syndecan-3 is a novel cocaine addiction resilience factor.

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1
Molecular and Integrative Neuroscience Department, The Scripps Research Institute, La Jolla, California 92037, USA.

Abstract

Proteoglycans like syndecan-3 have complex signaling roles in addition to their function as structural components of the extracellular matrix. Here, we show that syndecan-3 in the lateral hypothalamus has an unexpected new role in limiting compulsive cocaine intake. In particular, we observe that syndecan-3 null mice self-administer greater amounts of cocaine than wild-type mice. This effect can be rescued by re-expression of syndecan-3 in the lateral hypothalamus with an adeno-associated viral vector. Adeno-associated viral vector delivery of syndecan-3 to the lateral hypothalamus also reduces motivation for cocaine in normal mice. Syndecan-3 limits cocaine intake by modulating the effects of glial-cell-line-derived neurotrophic factor, which uses syndecan-3 as an alternative receptor. Our findings indicate syndecan-3-dependent signaling as a novel therapeutic target for the treatment of cocaine addiction.

PMID:
23736082
PMCID:
PMC3709481
DOI:
10.1038/ncomms2955
[Indexed for MEDLINE]
Free PMC Article
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