title: Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement.
abstract: Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drug-related behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortex-accumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies.
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Hearing
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Jakub
authors.initials: J
authors.lastname: Jedynak
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Ebner
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Anna
authors.initials: A
authors.lastname: Ingebretson
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Anders J
authors.initials: AJ
authors.lastname: Asp
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Fischer
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Clare
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Erin B
authors.initials: EB
authors.lastname: Larson
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455; Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN 55455; Department of Psychology, University of Minnesota, Minneapolis, MN 55455 tmhomas@umn.edu.
authors.forename: Mark John
authors.initials: MJ
authors.lastname: Thomas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D005838:Genotype; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D055620:Optical Phenomena; D021122:Protein Subunits / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D021122:Protein Subunits; D018091:Receptors, AMPA; D002443:Ceftriaxone; D009020:Morphine
keywords: GluA2-lacking AMPARs; ceftriaxone; nucleus accumbens; opiates; plasticity