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Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning

Drugs of abuse alter synaptic connections in the ‘reward circuit’ of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We dem...

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Autores principales: Mills, Fergil, Globa, Andrea K., Liu, Shuai, Cowan, Catherine M., Mobasser, Mahsan, Phillips, Anthony G., Borgland, Stephanie L., Bamji, Shernaz X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373847/
https://www.ncbi.nlm.nih.gov/pubmed/28192395
http://dx.doi.org/10.1038/nn.4503
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author Mills, Fergil
Globa, Andrea K.
Liu, Shuai
Cowan, Catherine M.
Mobasser, Mahsan
Phillips, Anthony G.
Borgland, Stephanie L.
Bamji, Shernaz X.
author_facet Mills, Fergil
Globa, Andrea K.
Liu, Shuai
Cowan, Catherine M.
Mobasser, Mahsan
Phillips, Anthony G.
Borgland, Stephanie L.
Bamji, Shernaz X.
author_sort Mills, Fergil
collection PubMed
description Drugs of abuse alter synaptic connections in the ‘reward circuit’ of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation (LTP) in the ventral tegmental area (VTA), and is recruited to the synaptic membrane of excitatory inputs onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a significant reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction.
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spelling pubmed-53738472017-10-01 Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning Mills, Fergil Globa, Andrea K. Liu, Shuai Cowan, Catherine M. Mobasser, Mahsan Phillips, Anthony G. Borgland, Stephanie L. Bamji, Shernaz X. Nat Neurosci Article Drugs of abuse alter synaptic connections in the ‘reward circuit’ of the brain, which leads to long-lasting behavioral changes that underlie addiction. Here we show that cadherin adhesion molecules play a critical role in mediating synaptic plasticity and behavioral changes driven by cocaine. We demonstrate that cadherin is essential for long-term potentiation (LTP) in the ventral tegmental area (VTA), and is recruited to the synaptic membrane of excitatory inputs onto dopaminergic neurons following cocaine-mediated behavioral conditioning. Furthermore, we show that stabilization of cadherin at the membrane of these synapses blocks cocaine-induced synaptic plasticity, leading to a significant reduction in conditioned place preference induced by cocaine. Our findings identify cadherins and associated molecules as targets of interest for understanding pathological plasticity associated with addiction. 2017-02-13 2017-04 /pmc/articles/PMC5373847/ /pubmed/28192395 http://dx.doi.org/10.1038/nn.4503 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Mills, Fergil
Globa, Andrea K.
Liu, Shuai
Cowan, Catherine M.
Mobasser, Mahsan
Phillips, Anthony G.
Borgland, Stephanie L.
Bamji, Shernaz X.
Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
title Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
title_full Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
title_fullStr Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
title_full_unstemmed Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
title_short Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
title_sort cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373847/
https://www.ncbi.nlm.nih.gov/pubmed/28192395
http://dx.doi.org/10.1038/nn.4503
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