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Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b-containing receptors
Open accessAbstract
Persistent relapse to addictive drugs constitutes the most challenging problem in addiction therapy, and is linked to impaired prefrontal cortex regulation of motivated behaviors involving the nucleus accumbens. Using a rat model of heroin addiction, we show that relapse requires long-term potentiation (LTP)-like increases in synaptic strength in the prefrontal cortex projection to the nucleus accumbens. The increased synaptic strength was paralleled by dendritic spine enlargement in accumbens spiny neurons and required up-regulated surface expression of NMDA2b-containing receptors (NR2B). Accordingly, blocking NR2B before reinstating heroin-seeking prevented the induction of LTP-like changes in spine remodeling and synaptic strength, and inhibited heroin relapse. These data show that LTP-like neuroplasticity in prefrontal-accumbens synapses is initiated by NR2B stimulation and strongly contributes to heroin relapse. Moreover, the data reveal NR2B-containing NMDA receptors as a previously unexplored therapeutic target for treating heroin addiction.
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Experience-dependent structural synaptic plasticity in the mammalian brain
Holtmaat, A., & Svoboda, K. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2699 · Cited by 1,934
Synaptic plasticity and addiction
Kauer, J. A., & Malenka, R. C. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2234 · Cited by 1,397
The glutamate homeostasis hypothesis of addiction
Kalivas, P. W. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2515 · Cited by 1,350
Self-citationFormation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving
Conrad, K. L., Tseng, K. Y., Uejima, J. L., Reimers, J. M., Heng, L.-J., Shaham, Y., Marinelli, M., & Wolf, M. E. (2008) · Nature · doi:10.1038/nature06995 · Cited by 790
Glutamate induces the rapid formation of spine head protrusions in hippocampal slice cultures
Richards, D. A., Mateos, J. M., Hugel, S., de Paola, V., Caroni, P., Gähwiler, B. H., & McKinney, R. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501881102 · Cited by 161
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The Neuroscience of Drug Reward and Addiction
Volkow, N. D., Michaelides, M., & Baler, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00014.2018 · Cited by 863
Scofield, M. D., Heinsbroek, J. A., Gipson, C. D., Kupchik, Y. M., Spencer, S., Smith, A. C. W., Roberts-Wolfe, D., & Kalivas, P. W. (2016) · Pharmacological Reviews · doi:10.1124/pr.116.012484 · Cited by 598
Self-citationBossert, J. M., Marchant, N. J., Calu, D. J., & Shaham, Y. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3120-y · Cited by 453
New medications for drug addiction hiding in glutamatergic neuroplasticity
Kalivas, P. W., & Volkow, N. D. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.46 · Cited by 349
Self-citationGq-DREADD Selectively Initiates Glial Glutamate Release and Inhibits Cue-induced Cocaine Seeking
Scofield, M. D., Boger, H. A., Smith, R. J., Li, H., Haydon, P. G., & Kalivas, P. W. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.02.016 · Cited by 197
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Metadata
- Authors
- Shen, H., Moussawi, K., Zhou, W., Toda, S., & Kalivas, P. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-11-14
- Volume
- 108
- Issue
- 48
- Pages
- 19407-19412
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2043978578
- Cited by
- 182
- References
- 6
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shen, H., Moussawi, K., Zhou, W., Toda, S., & Kalivas, P. W. (2011). Heroin relapse requires long-term potentiation-like plasticity mediated by NMDA2b-containing receptors. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1112052108
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
