• Stephanie R Ebner, Erin B Larson, Matthew C Hearing, Anna E Ingebretson, and Mark J Thomas.
• Department of Neuroscience, University of Minnesota, 3-432 McGuire Translational Research Facility 3-432, 2001 6th St SE, Minneapolis, MN 55455, USA.
• Neuroscience. 2018 Aug 1; 384: 340349340-349.

AbstractExperience-dependent synaptic plasticity is an important component of both learning and motivational disturbances found in addicted individuals. Here, we investigated the role of cocaine experience-dependent plasticity at excitatory synapses in the nucleus accumbens shell (NAcSh) in relapse-related behavior in mice with a history of volitional cocaine self-administration. Using an extinction/reinstatement paradigm of cocaine-seeking behavior, we demonstrate that cocaine-experienced mice with extinguished cocaine-seeking behavior show potentiation of synaptic strength at excitatory inputs onto NAcSh medium spiny neurons (MSNs). Conversely, we found that exposure to various distinct types of reinstating stimuli (cocaine, cocaine-associated cues, yohimbine "stress") after extinction can produce a relative depotentiation of NAcSh synapses that is strongly associated with the magnitude of cocaine-seeking behavior exhibited in response to these challenges. Furthermore, we show that these effects are due to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-specific mechanisms that differ depending on the nature and context of the reinstatement-inducing stimuli. Together, our findings identify common themes as well as differential mechanisms that are likely important for the ability of diverse environmental stimuli to drive relapse to addictive-like cocaine-seeking behavior.Copyright © 2018. Published by Elsevier Ltd.

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