Extinction and Reinstatement of Cocaine-seeking in Self-administering Mice is Associated with Bidirectional AMPAR-mediated Plasticity in the Nucleus Accumbens Shell. (1st August 2018)

• Record Type: Journal Article
• Authors: Ebner, Stephanie R.; Larson, Erin B.; Hearing, Matthew C.; Ingebretson, Anna E.; Thomas, Mark J.
• Is Part Of: Neuroscience. Volume 384(2018)
• Page Start: 340
• Page End: 349
• Publication Date: 2018-08-01
• Subjects: ACSF artificial cerebral spinal fluid -- AMPAR α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor -- COC cocaine -- CUE cocaine-associated discrete cue light -- D-AP5 D-aminophosphonovaleric acid -- FR1 fixed ratio 1 schedule of reinforcement -- GABA gamma-aminobutyric acid -- IU international units -- mEPSC mini excitatory post-synaptic current -- MSN medium spiny neuron -- NacSh nucleus accumbens shell -- NMDAR N-methyl-D-aspartate receptor -- NR non-reinstated mice -- PPR paired pulse ratio -- SA self-administration -- SAL saline -- YOH yohimbine; cocaine -- self-administration -- relapse -- plasticity -- nucleus accumbens -- AMPAR; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.05.043
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Cocaine self-administration produces synaptic plasticity in the nucleus accumbens. Extinction of cocaine-seeking behavior is associated with synaptic strengthening. Reinstated cocaine-seeking behavior is negatively correlated with synaptic strength. Different mechanisms are involved in reinstatement induced by different stimuli. Abstract: Experience-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.