Year: 2013
Type: article
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. The lateral hypothalamus is implicated in drug reward and addiction. Chen and colleagues find that in the lateral hypothalamus of mice, the proteoglycan syndecan-3 negatively regulates cocaine-seeking behaviour by modulating the effects of glial cell line-derived neurotrophic factor.
Source: Nature Communications
DOI: 10.1038/ncomms2955
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $6,990
Funders: McLean Hospital, Cleveland Clinic, Cleveland Clinic Foundation, Università degli Studi di Milano-Bicocca, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences
Awards: National Center: Multiscale Analysis of Genomic and Cellular Networks (MAGNet), G2002922973, G2221374616, G3422676241, G3593572123, G4234095926, Center for the Neurobiology of Addiction Treatment, G4945041102, Role of microRNAs in Behavioral Sensitization to Cocaine, G5163511262, G5306961167, G5629212314, G5953277874, G6017603234, Collaborative study on the systems biology of vulnerability to stress, G6674624523, G8022650662, G8241516228, G8545398155, G8646929396, G8725389344, G9000022848, G9000043204, G9000055871, G9000198522, NEUROPSYCHOPHARMACOLOGY: MULTIDISCIPLINARY TRAINING
OpenAlex ID: W2141817271