Research Article

Opioid-Induced Neuroplasticity: Insights from Animal Models

Zhaolin YangMcGill University*

* Corresponding author: [email protected]

Abstract

Synaptic plasticity is defined as the modification of the transmission of synapses. It has been proven to be strongly associated with learning. Thus, drug-evoked synaptic plasticity in brain reward circuits can establish persistent learning of addictive drugs, reflecting the neural basis underlying addiction. The mesolimbic dopamine pathway has been widely indicated to be strongly associated with opioid use disorder (OUD) and other drug addictions. The paper focuses on discussing the drug-evoked neural plasticity underlying two important stages called intoxication and withdrawal which are critical for addiction and reinstatement of drug use respectively. The paper first explores the neural basis of OUD, emphasizing drug-induced plasticity at glutamate and Gamma-aminobutyric acid (GABA) synapses on neurons of key substrates in the pathway and how they influence mesolimbic dopamine (DA) neuron transmission. Then, the review discussed withdrawal-induced neuroplasticity and reorganization of associated neuron circuits, which explain deficits led by withdrawal from opioid administration. An overall understanding of drug-evoked synaptic plasticity in key brain circuits in the development of addiction helps find possible therapeutic methods to prevent the initiation of OUD and reinstatement.

Keywords: opioid use disorder; mesolimbic pathway; dopamine; synaptic plasticity
Published: September 27, 2024
DOI: 10.54254/2753-7064/40/20242277
Volume: CHR Vol.40
pp. 137-143
Download PDF

References

  1. Strang, J., Volkow, N.D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G.F. and Walsh, S.L. (2020). Opioid use disorder. Nature reviews Disease primers, 6(1), 3.
  2. Cosci, F. and Chouinard, G. (2020). Acute and persistent withdrawal syndromes following discontinuation of psychotropic medications. Psychotherapy and psychosomatics, 89(5), 283-306.
  3. Koob, G.F. and Volkow, N.D. (2010). Neurocircuitry of addiction. Neuropsychopharmacology, 35(1), 217-238.
  4. Nestler, E.J., Hope, B.T. and Widnell, K.L. (1993). Drug addiction: a model for the molecular basis of neural plasticity. Neuron, 11(6), 995-1006.
  5. Jentsch, J.D. and Taylor, J.R. (1999). Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology, 146, 373-390.
  6. Kauer, J.A. and Malenka, R.C. (2007). Synaptic plasticity and addiction. Nature reviews neuroscience, 8(11), 844-858.
  7. Kalivas, P.W., LaLumiere, R.T., Knackstedt, L. and Shen, H. (2009). Glutamate transmission in addiction. Neuropharmacology, 56, 169-173.
  8. Chiamulera, C., Piva, A. and Abraham, W.C. (2021). Glutamate receptors and metaplasticity in addiction. Current Opinion in Pharmacology, 56, 39-45.
  9. Malenka, R.C. (1994). Synaptic plasticity in the hippocampus: LTP and LTD. Cell, 78(4), 535-538.
  10. Madsen, H.B., Brown, R.M. and Lawrence, A.J. (2012). Neuroplasticity in addiction: cellular and transcriptional perspectives. Frontiers in molecular neuroscience, 5, 99
  11. Simmler, L.D., Li, Y., Hadjas, L.C., Hiver, A., van Zessen, R. and Lüscher, C. (2022). Dual action of ketamine confines addiction liability. Nature, 608(7922), 368-373.
  12. Cheron, J. and Kerchove d’Exaerde, A.D. (2021). Drug addiction: from bench to bedside. Translational Psychiatry, 11(1), 424.
  13. Makino, H. and Malinow, R. (2009). AMPA receptor incorporation into synapses during LTP: the role of lateral movement and exocytosis. Neuron, 64(3), 381-390.
  14. Bouarab, C., Thompson, B. and Polter, A.M. (2019). VTA GABA neurons at the interface of stress and reward. Frontiers in neural circuits, 13, 78.
  15. Liu, Q.S., Pu, L. and Poo, M.M. (2005). Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature, 437(7061), 1027-1031.
  16. Chiu, C.Q. and Castillo, P.E. (2010). Endocannabinoid Mediated Long-Term Depression at Inhibitory Synapses. In Inhibitory Synaptic Plasticity (pp. 149-166). New York, NY: Springer New York.
  17. Ostroumov, A., Wittenberg, R.E., Kimmey, B.A., Taormina, M.B., Holden, W.M., McHugh, A.T. and Dani, J.A. (2020). Acute nicotine exposure alters ventral tegmental area inhibitory transmission and promotes diazepam consumption. Eneuro, 7(2).
  18. Vaquer-Alicea, A.D.C., Vázquez-Torres, R., Devarie-Hornedo, M., Vicenty-Padilla, J.C., Santos-Vera, B., María-Ríos, C. and Jiménez-Rivera, C.A. (2018). aPKC-mediated persistent increase in AMPA/NMDA ratio in the VTA participates in the neuroadaptive signal necessary to induce NAc synaptic plasticity after cocaine administration. Neuroscience, 392, 129-140.
  19. Wright, W.J. and Dong, Y. (2021). Silent synapses in cocaine-associated memory and beyond. Journal of Neuroscience, 41(45), 9275-9285.
  20. Lalchandani, R.R., van der Goes, M.S., Partridge, J.G. and Vicini, S. (2013). Dopamine D2 receptors regulate collateral inhibition between striatal medium spiny neurons. Journal of Neuroscience, 33(35), 14075-14086.
  21. Xiao, X., Deng, H., Furlan, A., Yang, T., Zhang, X., Hwang, G.R. and Li, B. (2020). A genetically defined compartmentalized striatal direct pathway for negative reinforcement. Cell, 183(1), 211-227.
  22. Stephenson-Jones, M., Yu, K., Ahrens, S., Tucciarone, J.M., van Huijstee, A.N., Mejia, L.A. and Li, B. (2016). A basal ganglia circuit for evaluating action outcomes. Nature, 539(7628), 289-293.
  23. Wang, W., Xie, X., Zhuang, X., Huang, Y., Tan, T., Gangal, H. and Wang, J. (2023). Striatal μ-opioid receptor activation triggers direct-pathway GABAergic plasticity and induces negative affect. Cell reports, 42(2).
  24. McDevitt, D.S., Jonik, B., and Graziane, N.M. (2019). Morphine differentially alters the synaptic and intrinsic properties of D1R-and D2R-expressing medium spiny neurons in the nucleus accumbens. Frontiers in Synaptic Neuroscience, 11, 35.
  25. Giannotti, G., Gong, S., Fayette, N., Heinsbroek, J.A., Orfila, J.E., Herson, P.S. and Peters, J. (2021). Extinction blunts paraventricular thalamic contributions to heroin relapse. Cell reports, 36(8).