Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Matthew C. Hearing; Jakub Jedynak; Stephanie R. Ebner; Anna Ingebretson; Anders J. Asp; Rachel A. Fischer; Clare Schmidt; Erin B. Larson; Mark John Thomas

doi:10.1073/pnas.1519248113

Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Matthew C. Hearing, Jakub Jedynak, Stephanie R. Ebner, Anna Ingebretson, Anders J. Asp, Rachel A. Fischer, Clare Schmidt, Erin B. Larson, Mark John Thomas

Neuroscience

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

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 drugrelated 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 cortexaccumbens 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.

Original language	English (US)
Pages (from-to)	757-762
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	3
DOIs	https://doi.org/10.1073/pnas.1519248113
State	Published - Jan 19 2016

Bibliographical note

Funding Information:
The MnDRIVE Optogenetics Core at the University of Minnesota provided invaluable technical support. This work was supported by funding from the National Institute on Drug Abuse Grants R01 DA019666, K02 DA035459 (to M.J.T.), K99 DA038706 (to M.C.H.), and T32 DA007234 (to A.I. and S.R.E.); the MnDRIVE Initiative on Brain Conditions; and the Breyer-Longden Family Research Fund.

Keywords

Ceftriaxone
Glua2-lacking AMPARs
Nucleus accumbens
Opiates
Plasticity

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Hearing, M. C., Jedynak, J., Ebner, S. R., Ingebretson, A., Asp, A. J., Fischer, R. A., Schmidt, C., Larson, E. B., & Thomas, M. J. (2016). Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement. Proceedings of the National Academy of Sciences of the United States of America, 113(3), 757-762. https://doi.org/10.1073/pnas.1519248113

Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement. / Hearing, Matthew C.; Jedynak, Jakub; Ebner, Stephanie R. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 3, 19.01.2016, p. 757-762.

Research output: Contribution to journal › Article › peer-review

Hearing, MC, Jedynak, J, Ebner, SR, Ingebretson, A, Asp, AJ, Fischer, RA, Schmidt, C, Larson, EB & Thomas, MJ 2016, 'Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 3, pp. 757-762. https://doi.org/10.1073/pnas.1519248113

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Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement

Abstract

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