title: Cadherins mediate cocaine-induced synaptic plasticity and behavioral conditioning.
abstract: Drugs of abuse alter synaptic connections in the reward circuitry 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 in the ventral tegmental area and is recruited to the synaptic membranes of excitatory synapses 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 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.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Fergil
authors.initials: F
authors.lastname: Mills
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Andrea K
authors.identifier: http://orcid.org/0000-0001-6557-4679
authors.initials: AK
authors.lastname: Globa
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Cowan
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mahsan
authors.initials: M
authors.lastname: Mobasser
authors.affiliation: Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
authors.affiliation: Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Borgland
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shernaz X
authors.initials: SX
authors.lastname: Bamji
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000502:physiology*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D015820:Cadherins; D003042:Cocaine; D018091:Receptors, AMPA