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Cocaine-induced projection-specific and cell type-specific adaptations in the nucleus accumbens

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Abstract

Cocaine craving, seeking, and relapse are mediated, in part, by cocaine-induced adaptive changes in the brain reward circuits. The nucleus accumbens (NAc) integrates and prioritizes different emotional and motivational inputs to the reward system by processing convergent glutamatergic projections from the medial prefrontal cortex, basolateral amygdala, ventral hippocampus, and other limbic and paralimbic brain regions. Medium spiny neurons (MSNs) are the principal projection neurons in the NAc, which can be divided into two major subpopulations, namely dopamine receptor D1- versus D2-expressing MSNs, with complementing roles in reward-associated behaviors. After cocaine experience, NAc MSNs exhibit complex and differential adaptations dependent on cocaine regimen, withdrawal time, cell type, location (NAc core versus shell), and related input and output projections, or any combination of these factors. Detailed characterization of these cellular adaptations has been greatly facilitated by the recent development of optogenetic/chemogenetic techniques combined with transgenic tools. In this review, we discuss such cell type- and projection-specific adaptations induced by cocaine experience. Specifically, (1) D1 and D2 NAc MSNs frequently exhibit differential adaptations in spinogenesis, glutamatergic receptor trafficking, and intrinsic membrane excitability, (2) cocaine experience differentially changes the synaptic transmission at different afferent projections onto NAc MSNs, (3) cocaine-induced NAc adaptations exhibit output specificity, e.g., being different at NAc-ventral pallidum versus NAc-ventral tegmental area synapses, and (4) the input, output, subregion, and D1/D2 cell type may together determine cocaine-induced circuit plasticity in the NAc. In light of the projection- and cell-type specificity, we also briefly discuss ensemble and circuit mechanisms contributing to cocaine craving and relapse after drug withdrawal.

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Fig. 1: Cocaine-induced projection- and cell type-specific neural adaptations in the NAc circuit.

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References

  1. Hyman SE. Addiction to cocaine and amphetamine. Neuron. 1996;16:901–4.

    Article  CAS  PubMed  Google Scholar 

  2. Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu Rev Neurosci. 2006;29:565–98.

    Article  CAS  PubMed  Google Scholar 

  3. Hyman SE. Addiction: a disease of learning and memory. Am J Psychiatry. 2005;162:1414–22.

    Article  PubMed  Google Scholar 

  4. Sesack SR, Grace AA. Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology. 2010;35:27–47.

    Article  PubMed  Google Scholar 

  5. Mogenson GJ, Jones DL, Yim CY. From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol. 1980;14:69–97.

    Article  CAS  PubMed  Google Scholar 

  6. Kelley AE. Memory and addiction: shared neural circuitry and molecular mechanisms. Neuron. 2004;44:161–79.

    Article  CAS  PubMed  Google Scholar 

  7. Cox J, Witten IB. Striatal circuits for reward learning and decision-making. Nat Rev Neurosci. 2019;20:482–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pettit HO, Ettenberg A, Bloom FE, Koob GF. Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology. 1984;84:167–73.

    Article  CAS  PubMed  Google Scholar 

  9. Roberts DC, Koob GF, Klonoff P, Fibiger HC. Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav. 1980;12:781–7.

    Article  CAS  PubMed  Google Scholar 

  10. Cador M, Bjijou Y, Stinus L. Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine. Neuroscience. 1995;65:385–95.

    Article  CAS  PubMed  Google Scholar 

  11. Paulson PE, Robinson TE. Sensitization to systemic amphetamine produces an enhanced locomotor response to a subsequent intra-accumbens amphetamine challenge in rats. Psychopharmacology. 1991;104:140–1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kalivas PW. Glutamate systems in cocaine addiction. Curr Opin Pharmacol. 2004;4:23–29.

    Article  CAS  PubMed  Google Scholar 

  13. Tzschentke TM, Schmidt WJ. Glutamatergic mechanisms in addiction. Mol Psychiatry. 2003;8:373–82.

    Article  CAS  PubMed  Google Scholar 

  14. Ito R, Robbins TW, Everitt BJ. Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat Neurosci. 2004;7:389–97.

    Article  CAS  PubMed  Google Scholar 

  15. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35:217–38.

    Article  PubMed  Google Scholar 

  16. Wolf ME. Synaptic mechanisms underlying persistent cocaine craving. Nat Rev Neurosci. 2016;17:351–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Scofield MD, Heinsbroek JA, Gipson CD, Kupchik YM, Spencer S, Smith AC, et al. The nucleus accumbens: mechanisms of addiction across drug classes reflect the importance of glutamate homeostasis. Pharm Rev. 2016;68:816–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011;34:441–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lobo MK, Nestler EJ. The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons. Front Neuroanat. 2011;5:41.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Smith RJ, Lobo MK, Spencer S, Kalivas PW. Cocaine-induced adaptations in D1 and D2 accumbens projection neurons (a dichotomy not necessarily synonymous with direct and indirect pathways). Curr Opin Neurobiol. 2013;23:546–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tritsch NX, Sabatini BL. Dopaminergic modulation of synaptic transmission in cortex and striatum. Neuron. 2012;76:33–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kawaguchi Y, Wilson CJ, Augood SJ, Emson PC. Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci. 1995;18:527–35.

    Article  CAS  PubMed  Google Scholar 

  23. Tepper JM, Tecuapetla F, Koos T, Ibanez-Sandoval O. Heterogeneity and diversity of striatal GABAergic interneurons. Front Neuroanat. 2010;4:150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Silberberg G, Bolam JP. Local and afferent synaptic pathways in the striatal microcircuitry. Curr Opin Neurobiol. 2015;33:182–7.

    Article  CAS  PubMed  Google Scholar 

  25. Tepper JM, Koos T, Ibanez-Sandoval O, Tecuapetla F, Faust TW, Assous M. Heterogeneity and diversity of striatal GABAergic interneurons: update 2018. Front Neuroanat. 2018;12:91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schall TA, Wright WJ, Dong Y. Nucleus accumbens fast-spiking interneurons in motivational and addictive behaviors. Mol Psychiatry. 2021;26:234–246.

  27. White FJ, Hu XT, Zhang XF, Wolf ME. Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. J Pharm Exp Ther. 1995;273:445–54.

    CAS  Google Scholar 

  28. Wolf ME. The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog Neurobiol. 1998;54:679–720.

    Article  CAS  PubMed  Google Scholar 

  29. Robinson TE, Gorny G, Mitton E, Kolb B. Cocaine self-administration alters the morphology of dendrites and dendritic spines in the nucleus accumbens and neocortex. Synapse. 2001;39:257–66.

    Article  CAS  PubMed  Google Scholar 

  30. Robinson TE, Kolb B. Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology. 2004;47:33–46.

    Article  CAS  PubMed  Google Scholar 

  31. Russo SJ, Dietz DM, Dumitriu D, Morrison JH, Malenka RC, Nestler EJ. The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends Neurosci. 2010;33:267–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Golden SA, Russo SJ. Mechanisms of psychostimulant-induced structural plasticity. Cold Spring Harb Perspect Med. 2012;2:1–25.

  33. Christian DT, Wang X, Chen EL, Sehgal LK, Ghassemlou MN, Miao JJ, et al. Dynamic alterations of rat nucleus accumbens dendritic spines over 2 months of abstinence from extended-access cocaine self-administration. Neuropsychopharmacology. 2017;42:748–56.

    Article  CAS  PubMed  Google Scholar 

  34. Huang YH, Lin Y, Mu P, Lee BR, Brown TE, Wayman G, et al. In vivo cocaine experience generates silent synapses. Neuron. 2009;63:40–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Huang YH, Schluter OM, Dong Y. Silent synapses speak up: updates of the neural rejuvenation hypothesis of drug addiction. Neuroscientist. 2015;21:451–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Koya E, Cruz FC, Ator R, Golden SA, Hoffman AF, Lupica CR, et al. Silent synapses in selectively activated nucleus accumbens neurons following cocaine sensitization. Nat Neurosci. 2012;15:1556–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Whitaker LR, Carneiro de Oliveira PE, McPherson KB, Fallon RV, Planeta CS, Bonci A, et al. Associative learning drives the formation of silent synapses in neuronal ensembles of the nucleus accumbens. Biol Psychiatry. 2016;80:246–56.

    Article  PubMed  Google Scholar 

  38. Wright WJ, Dong Y. Psychostimulant-induced adaptations in nucleus accumbens glutamatergic transmission. Cold Spring Harb Perspect Med. 2020;10:a039255.

    Article  CAS  PubMed  Google Scholar 

  39. Lee BR, Ma YY, Huang YH, Wang X, Otaka M, Ishikawa M, et al. Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving. Nat Neurosci. 2013;16:1644–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ma YY, Lee BR, Wang X, Guo C, Liu L, Cui R, et al. Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections. Neuron. 2014;83:1453–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Graziane NM, Sun S, Wright WJ, Jang D, Liu Z, Huang YH, et al. Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses. Nat Neurosci. 2016;19:915–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Brown TE, Lee BR, Mu P, Ferguson D, Dietz D, Ohnishi YN, et al. A silent synapse-based mechanism for cocaine-induced locomotor sensitization. J Neurosci. 2011;31:8163–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Terrier J, Luscher C, Pascoli V. Cell-type specific insertion of GluA2-lacking AMPARs with cocaine exposure leading to sensitization, cue-induced seeking, and incubation of craving. Neuropsychopharmacology. 2016;41:1779–89.

    Article  CAS  PubMed  Google Scholar 

  44. Wang J, Li KL, Shukla A, Beroun A, Ishikawa M, Huang X, et al. Cocaine triggers astrocyte-mediated synaptogenesis. Biol Psychiatry. 2021;89:386–397.

  45. Wright WJ, Graziane NM, Neumann PA, Hamilton PJ, Cates HM, Fuerst L, et al. Silent synapses dictate cocaine memory destabilization and reconsolidation. Nat Neurosci. 2020;23:32–46.

    Article  CAS  PubMed  Google Scholar 

  46. Conrad KL, Tseng KY, Uejima JL, Reimers JM, Heng LJ, Shaham Y, et al. Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving. Nature. 2008;454:118–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. McCutcheon JE, Loweth JA, Ford KA, Marinelli M, Wolf ME, Tseng KY. Group I mGluR activation reverses cocaine-induced accumulation of calcium-permeable AMPA receptors in nucleus accumbens synapses via a protein kinase C-dependent mechanism. J Neurosci. 2011;31:14536–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Loweth JA, Reimers JM, Caccamise A, Stefanik MT, Woo KKY, Chauhan NM, et al. mGlu1 tonically regulates levels of calcium-permeable AMPA receptors in cultured nucleus accumbens neurons through retinoic acid signaling and protein translation. Eur J Neurosci. 2019;50:2590–601.

    Article  PubMed  Google Scholar 

  49. Loweth JA, Scheyer AF, Milovanovic M, LaCrosse AL, Flores-Barrera E, Werner CT, et al. Synaptic depression via mGluR1 positive allosteric modulation suppresses cue-induced cocaine craving. Nat Neurosci. 2014;17:73–80.

    Article  CAS  PubMed  Google Scholar 

  50. Scheyer AF, Wolf ME, Tseng KY. A protein synthesis-dependent mechanism sustains calcium-permeable AMPA receptor transmission in nucleus accumbens synapses during withdrawal from cocaine self-administration. J Neurosci. 2014;34:3095–3100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Valjent E, Bertran-Gonzalez J, Hervé D, Fisone G, Girault J-A. Looking BAC at striatal signaling: cell-specific analysis in new transgenic mice. Trends Neurosci. 2009;32:538–47.

    Article  CAS  PubMed  Google Scholar 

  52. Ade KK, Wan Y, Chen M, Gloss B, Calakos N. An improved BAC transgenic fluorescent reporter line for sensitive and specific identification of striatonigral medium spiny neurons. Front Syst Neurosci. 2011;5:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kim J, Park BH, Lee JH, Park SK, Kim JH. Cell type-specific alterations in the nucleus accumbens by repeated exposures to cocaine. Biol Psychiatry. 2011;69:1026–34.

    Article  CAS  PubMed  Google Scholar 

  54. Lee KW, Kim Y, Kim AM, Helmin K, Nairn AC, Greengard P. Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens. Proc Natl Acad Sci USA. 2006;103:3399–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pardo-Garcia TR, Garcia-Keller C, Penaloza T, Richie CT, Pickel J, Hope BT, et al. Ventral pallidum is the primary target for accumbens D1 projections driving cocaine seeking. J Neurosci. 2019;39:2041–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Heinsbroek JA, Bobadilla AC, Dereschewitz E, Assali A, Chalhoub RM, Cowan CW, et al. Opposing regulation of cocaine seeking by glutamate and GABA neurons in the ventral pallidum. Cell Rep. 2020;30:2018–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kupchik YM, Brown RM, Heinsbroek JA, Lobo MK, Schwartz DJ, Kalivas PW. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections. Nat Neurosci. 2015;18:1230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Calipari ES, Bagot RC, Purushothaman I, Davidson TJ, Yorgason JT, Pena CJ, et al. In vivo imaging identifies temporal signature of D1 and D2 medium spiny neurons in cocaine reward. Proc Natl Acad Sci USA. 2016;113:2726–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lobo MK, Covington HE 3rd, Chaudhury D, Friedman AK, Sun H, Damez-Werno D, et al. Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science. 2010;330:385–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yawata S, Yamaguchi T, Danjo T, Hikida T, Nakanishi S. Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens. Proc Natl Acad Sci USA. 2012;109:12764–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Bock R, Shin JH, Kaplan AR, Dobi A, Markey E, Kramer PF, et al. Strengthening the accumbal indirect pathway promotes resilience to compulsive cocaine use. Nat Neurosci. 2013;16:632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bamford NS, Wightman RM, Sulzer D. Dopamine’s effects on corticostriatal synapses during reward-based behaviors. Neuron. 2018;97:494–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Barbera G, Liang B, Zhang L, Gerfen CR, Culurciello E, Chen R, et al. Spatially compact neural clusters in the dorsal striatum encode locomotion relevant information. Neuron. 2016;92:202–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hikida T, Kimura K, Wada N, Funabiki K, Nakanishi S. Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior. Neuron. 2010;66:896–907.

    Article  CAS  PubMed  Google Scholar 

  65. Iino Y, Sawada T, Yamaguchi K, Tajiri M, Ishii S, Kasai H, et al. Dopamine D2 receptors in discrimination learning and spine enlargement. Nature. 2020;579:555–60.

    Article  CAS  PubMed  Google Scholar 

  66. Pascoli V, Turiault M, Lüscher C. Reversal of cocaine-evoked synaptic potentiation resets drug-induced adaptive behaviour. Nature. 2012;481:71–5.

    Article  CAS  Google Scholar 

  67. MacAskill AF, Cassel JM, Carter AG. Cocaine exposure reorganizes cell type- and input-specific connectivity in the nucleus accumbens. Nat Neurosci. 2014;17:1198–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pascoli V, Terrier J, Espallergues J, Valjent E, O’Connor EC, Luscher C. Contrasting forms of cocaine-evoked plasticity control components of relapse. Nature. 2014;509:459–64.

    Article  CAS  PubMed  Google Scholar 

  69. Roberts-Wolfe D, Bobadilla AC, Heinsbroek JA, Neuhofer D, Kalivas PW. Drug refraining and seeking potentiate synapses on distinct populations of accumbens medium spiny neurons. J Neurosci. 2018;38:7100–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Roberts-Wolfe DJ, Heinsbroek JA, Spencer SM, Bobadilla AC, Smith ACW, Gipson CD, et al. Transient synaptic potentiation in nucleus accumbens shell during refraining from cocaine seeking. Addict Biol. 2020;25:e12759.

    Article  PubMed  Google Scholar 

  71. Hollander JA, Carelli RM. Cocaine-associated stimuli increase cocaine seeking and activate accumbens core neurons after abstinence. J Neurosci. 2007;27:3535–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Wheeler RA, Carelli RM. Dissecting motivational circuitry to understand substance abuse. Neuropharmacology. 2009;56:149–59.

    Article  CAS  PubMed  Google Scholar 

  73. Carelli RM, King VC, Hampson RE, Deadwyler SA. Firing patterns of nucleus accumbens neurons during cocaine self-administration in rats. Brain Res. 1993;626:14–22.

    Article  CAS  PubMed  Google Scholar 

  74. Salgado S, Kaplitt MG. The nucleus accumbens: a comprehensive review. Stereotact Funct Neurosurg. 2015;93:75–93.

    Article  PubMed  Google Scholar 

  75. Britt JP, Benaliouad F, McDevitt RA, Stuber GD, Wise RA, Bonci A. Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron. 2012;76:790–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ma L, Chen W, Yu D, Han Y. Brain-wide wapping of afferent inputs to accumbens nucleus core subdomains and accumbens nucleus subnuclei. Front Syst Neurosci. 2020;14:15.

    Article  PubMed  PubMed Central  Google Scholar 

  77. French S, Totterdell S. Individual nucleus accumbens-projection neurons receive both basolateral amygdala and ventral subicular afferents in rats. Neuroscience. 2003;119:19–31.

    Article  CAS  PubMed  Google Scholar 

  78. French SJ, Totterdell S. Hippocampal and prefrontal cortical inputs monosynaptically converge with individual projection neurons of the nucleus accumbens. J Comp Neurol. 2002;446:151–65.

    Article  PubMed  Google Scholar 

  79. Finch DM. Neurophysiology of converging synaptic inputs from the rat prefrontal cortex, amygdala, midline thalamus, and hippocampal formation onto single neurons of the caudate/putamen and nucleus accumbens. Hippocampus. 1996;6:495–512.

    Article  CAS  PubMed  Google Scholar 

  80. Groenewegen HJ, Wright CI, Beijer AV, Voorn P. Convergence and segregation of ventral striatal inputs and outputs. Ann N Y Acad Sci. 1999;877:49–63.

    Article  CAS  PubMed  Google Scholar 

  81. Xia SH, Yu J, Huang X, Sesack SR, Huang YH, Schluter OM, et al. Cortical and thalamic interaction with amygdala-to-accumbens synapses. J Neurosci. 2020;40:7119–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ragozzino ME. The contribution of the medial prefrontal cortex, orbitofrontal cortex, and dorsomedial striatum to behavioral flexibility. Ann N Y Acad Sci. 2007;1121:355–75.

    Article  PubMed  Google Scholar 

  83. Rushworth MF, Noonan MP, Boorman ED, Walton ME, Behrens TE. Frontal cortex and reward-guided learning and decision-making. Neuron. 2011;70:1054–69.

    Article  CAS  PubMed  Google Scholar 

  84. Jentsch JD, Ashenhurst JR, Cervantes MC, Groman SM, James AS, Pennington ZT. Dissecting impulsivity and its relationships to drug addictions. Ann N Y Acad Sci. 2014;1327:1–26.

    PubMed  PubMed Central  Google Scholar 

  85. McFarland K, Kalivas PW. The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci. 2001;21:8655–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Stefanik MT, Moussawi K, Kupchik YM, Smith KC, Miller RL, Huff ML, et al. Optogenetic inhibition of cocaine seeking in rats. Addict Biol. 2013;18:50–53.

    Article  CAS  PubMed  Google Scholar 

  87. Fuchs RA, Evans KA, Ledford CC, Parker MP, Case JM, Mehta RH, et al. The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine seeking in rats. Neuropsychopharmacology. 2005;30:296–309.

    Article  CAS  PubMed  Google Scholar 

  88. Peters J, LaLumiere RT, Kalivas PW. Infralimbic prefrontal cortex is responsible for inhibiting cocaine seeking in extinguished rats. J Neurosci. 2008;28:6046–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. LaLumiere RT, Smith KC, Kalivas PW. Neural circuit competition in cocaine-seeking: roles of the infralimbic cortex and nucleus accumbens shell. Eur J Neurosci. 2012;35:614–22.

    Article  PubMed  PubMed Central  Google Scholar 

  90. LaLumiere RT, Niehoff KE, Kalivas PW. The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration. Learn Mem. 2010;17:168–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Augur IF, Wyckoff AR, Aston-Jones G, Kalivas PW, Peters J. Chemogenetic activation of an extinction neural circuit reduces cue-induced reinstatement of cocaine seeking. J Neurosci. 2016;36:10174–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Cameron CM, Murugan M, Choi JY, Engel EA, Witten IB. Increased cocaine motivation is associated with degraded spatial and temporal representations in IL-NAc neurons. Neuron. 2019;103:80–91.

  93. Suska A, Lee BR, Huang YH, Dong Y, Schluter OM. Selective presynaptic enhancement of the prefrontal cortex to nucleus accumbens pathway by cocaine. Proc Natl Acad Sci USA. 2013;110:713–8.

    Article  CAS  PubMed  Google Scholar 

  94. MacAskill AF, Little JP, Cassel JM, Carter AG. Subcellular connectivity underlies pathway-specific signaling in the nucleus accumbens. Nat Neurosci. 2012;15:1624–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Carelli RM, Williams JG, Hollander JA. Basolateral amygdala neurons encode cocaine self-administration and cocaine-associated cues. J Neurosci. 2003;23:8204–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Janak PH, Tye KM. From circuits to behaviour in the amygdala. Nature. 2015;517:284–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Setlow B, Holland PC, Gallagher M. Disconnection of the basolateral amygdala complex and nucleus accumbens impairs appetitive pavlovian second-order conditioned responses. Behav Neurosci. 2002;116:267–75.

    Article  PubMed  Google Scholar 

  98. Shiflett MW, Balleine BW. At the limbic–motor interface: disconnection of basolateral amygdala from nucleus accumbens core and shell reveals dissociable components of incentive motivation. Eur J Neurosci. 2010;32:1735–43.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Stuber GD, Sparta DR, Stamatakis AM, van Leeuwen WA, Hardjoprajitno JE, Cho S, et al. Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature. 2011;475:377–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Millan EZ, Kim HA, Janak PH. Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior. Neuroscience. 2017;360:106–17.

    Article  CAS  PubMed  Google Scholar 

  101. Wang Y, Liu Z, Cai L, Guo R, Dong Y, Huang YH. A critical role of basolateral amygdala-to-nucleus accumbens projection in sleep regulation of reward seeking. Biol Psychiatry. 2020;87:954–66.

    Article  CAS  PubMed  Google Scholar 

  102. Di Ciano P, Everitt BJ. Direct interactions between the basolateral amygdala and nucleus accumbens core underlie cocaine-seeking behavior by rats. J Neurosci. 2004;24:7167–73.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Ambroggi F, Ishikawa A, Fields HL, Nicola SM. Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons. Neuron. 2008;59:648–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Stefanik MT, Kalivas PW. Optogenetic dissection of basolateral amygdala projections during cue-induced reinstatement of cocaine seeking. Front Behav Neurosci. 2013;7:213.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Baimel C, McGarry LM, Carter AG. The projection targets of medium spiny neurons govern cocaine-evoked synaptic plasticity in the nucleus accumbens. Cell Rep. 2019;28:2256–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Ma YY, Wang X, Huang Y, Marie H, Nestler EJ, Schluter OM, et al. Re-silencing of silent synapses unmasks anti-relapse effects of environmental enrichment. Proc Natl Acad Sci USA. 2016;113:5089–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Purgianto A, Weinfeld ME, Wolf ME. Prolonged withdrawal from cocaine self‐administration affects prefrontal cortex‐and basolateral amygdala–nucleus accumbens core circuits but not accumbens GABAergic local interneurons. Addiction Biol. 2017;22:1682–94.

    Article  CAS  Google Scholar 

  108. Fanselow MS, Dong HW. Are the dorsal and ventral hippocampus functionally distinct structures? Neuron. 2010;65:7–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Trouche S, Koren V, Doig NM, Ellender TJ, El-Gaby M, Lopes-Dos-Santos V, et al. A hippocampus-accumbens tripartite neuronal motif guides appetitive memory in space. Cell. 2019;176:1393–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ito R, Robbins TW, Pennartz CM, Everitt BJ. Functional interaction between the hippocampus and nucleus accumbens shell is necessary for the acquisition of appetitive spatial context conditioning. J Neurosci. 2008;28:6950–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Lansink CS, Goltstein PM, Lankelma JV, McNaughton BL, Pennartz CM. Hippocampus leads ventral striatum in replay of place-reward information. PLoS Biol. 2009;7:e1000173.

    Article  PubMed  PubMed Central  Google Scholar 

  112. LeGates TA, Kvarta MD, Tooley JR, Francis TC, Lobo MK, Creed MC, et al. Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses. Nature. 2018;564:258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Abela AR, Duan Y, Chudasama Y. Hippocampal interplay with the nucleus accumbens is critical for decisions about time. Eur J Neurosci. 2015;42:2224–33.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Yang AK, Mendoza JA, Lafferty CK, Lacroix F, Britt JP. Hippocampal input to the nucleus accumbens shell enhances food palatability. Biol Psychiatry. 2020;87:597–608.

    Article  CAS  PubMed  Google Scholar 

  115. Zhou K, Zhu Y. The paraventricular thalamic nucleus: a key hub of neural circuits underlying drug addiction. Pharm Res. 2019;142:70–6.

    Article  Google Scholar 

  116. Berendse HW, Groenewegen HJ. Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum. J Comp Neurol. 1990;299:187–228.

    Article  CAS  PubMed  Google Scholar 

  117. O’Donnell P, Lavın A, Enquist LW, Grace AA, Card JP. Interconnected parallel circuits between rat nucleus accumbens and thalamus revealed by retrograde transynaptic transport of pseudorabies virus. J Neurosci. 1997;17:2143–67.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Otake K, Nakamura Y. Single midline thalamic neurons projecting to both the ventral striatum and the prefrontal cortex in the rat. Neuroscience. 1998;86:635–49.

    Article  CAS  PubMed  Google Scholar 

  119. Pinto A, Jankowski M, Sesack SR. Projections from the paraventricular nucleus of the thalamus to the rat prefrontal cortex and nucleus accumbens shell: ultrastructural characteristics and spatial relationships with dopamine afferents. J Comp Neurol. 2003;459:142–55.

    Article  PubMed  Google Scholar 

  120. Vertes RP, Hoover WB. Projections of the paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat. J Comp Neurol. 2008;508:212–37.

    Article  PubMed  Google Scholar 

  121. Campus P, Covelo IR, Kim Y, Parsegian A, Kuhn BN, Lopez SA, et al. The paraventricular thalamus is a critical mediator of top-down control of cue-motivated behavior in rats. Elife. 2019;8:e49041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Otis JM, Zhu M, Namboodiri VMK, Cook CA, Kosyk O, Matan AM, et al. Paraventricular thalamus projection neurons integrate cortical and hypothalamic signals for cue-reward processing. Neuron. 2019;103:423–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Zhu Y, Wienecke CF, Nachtrab G, Chen X. A thalamic input to the nucleus accumbens mediates opiate dependence. Nature. 2016;530:219–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Young CD, Deutch AY. The effects of thalamic paraventricular nucleus lesions on cocaine-induced locomotor activity and sensitization. Pharmacol Biochem Behav. 1998;60:753–8.

    Article  CAS  PubMed  Google Scholar 

  125. Browning JR, Jansen HT, Sorg BA. Inactivation of the paraventricular thalamus abolishes the expression of cocaine conditioned place preference in rats. Drug Alcohol Depend. 2014;134:387–90.

    Article  CAS  PubMed  Google Scholar 

  126. James MH, Charnley JL, Jones E, Levi EM, Yeoh JW, Flynn JR, et al. Cocaine-and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour. PLoS ONE. 2010;5:e12980.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Neumann PA, Wang Y, Yan Y, Wang Y, Ishikawa M, Cui R, et al. Cocaine-induced synaptic alterations in thalamus to nucleus accumbens projection. Neuropsychopharmacology. 2016;41:2399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Deutch AY, Bubser M, Young CD. Psychostimulant-induced Fos protein expression in the thalamic paraventricular nucleus. J Neurosci. 1998;18:10680–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. James M, Charnley J, Flynn J, Smith D, Dayas C. Propensity to ‘relapse’ following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei. Neuroscience. 2011;199:235–42.

    Article  CAS  PubMed  Google Scholar 

  130. Matzeu A, Cauvi G, Kerr TM, Weiss F, Martin‐Fardon R. The paraventricular nucleus of the thalamus is differentially recruited by stimuli conditioned to the availability of cocaine versus palatable food. Addiction Biol. 2017;22:70–77.

    Article  CAS  Google Scholar 

  131. Durand GM, Kovalchuk Y, Konnerth A. Long-term potentiation and functional synapse induction in developing hippocampus. Nature. 1996;381:71–75.

    Article  CAS  PubMed  Google Scholar 

  132. Kerchner GA, Nicoll RA. Silent synapses and the emergence of a postsynaptic mechanism for LTP. Nat Rev Neurosci. 2008;9:813–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Hanse E, Seth H, Riebe I. AMPA-silent synapses in brain development and pathology. Nat Rev Neurosci. 2013;14:839–50.

    Article  CAS  PubMed  Google Scholar 

  134. Brown TE, Lee BR, Ryu V, Herzog T, Czaja K, Dong Y. Reducing hippocampal cell proliferation in the adult rat does not prevent the acquisition of cocaine-induced conditioned place preference. Neurosci Lett. 2010;481:41–46.

    Article  CAS  PubMed  Google Scholar 

  135. Dong Y, Nestler EJ. The neural rejuvenation hypothesis of cocaine addiction. Trends Pharm Sci. 2014;35:374–83.

    Article  CAS  PubMed  Google Scholar 

  136. Waites CL, Craig AM, Garner CC. Mechanisms of vertebrate synaptogenesis. Annu Rev Neurosci. 2005;28:251–74.

    Article  CAS  PubMed  Google Scholar 

  137. Carlezon WA Jr., Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N, et al. Regulation of cocaine reward by CREB. Science. 1998;282:2272–5.

    Article  CAS  PubMed  Google Scholar 

  138. Chao J, Nestler EJ. Molecular neurobiology of drug addiction. Annu Rev Med. 2004;55:113–32.

    Article  CAS  PubMed  Google Scholar 

  139. Grueter BA, Robison AJ, Neve RL, Nestler EJ, Malenka RC. ∆ FosB differentially modulates nucleus accumbens direct and indirect pathway function. Proc Natl Acad Sci USA. 2013;110:1923–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Nestler EJ. Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci. 2001;2:119–28.

    Article  CAS  PubMed  Google Scholar 

  141. Salery M, Trifilieff P, Caboche J, Vanhoutte P. From signaling molecules to circuits and behaviors: cell-type-specific adaptations to psychostimulant exposure in the striatum. Biol Psychiatry. 2020;87:944–53.

    Article  CAS  PubMed  Google Scholar 

  142. Shi S, Hayashi Y, Esteban JA, Malinow R. Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell. 2001;105:331–43.

    Article  CAS  PubMed  Google Scholar 

  143. Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell. 2002;110:443–55.

    Article  CAS  PubMed  Google Scholar 

  144. McCutcheon JE, Wang X, Tseng KY, Wolf ME, Marinelli M. Calcium-permeable AMPA receptors are present in nucleus accumbens synapses after prolonged withdrawal from cocaine self-administration but not experimenter-administered cocaine. J Neurosci. 2011;31:5737–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Turner BD, Rook JM, Lindsley CW, Conn PJ, Grueter BA. mGlu 1 and mGlu 5 modulate distinct excitatory inputs to the nucleus accumbens shell. Neuropsychopharmacology. 2018;43:2075–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Turner BD, Kashima DT, Manz KM, Grueter CA, Grueter BA. Synaptic plasticity in the nucleus accumbens: lessons learned from experience. ACS Chem Neurosci. 2017;9:2114–26.

    Article  Google Scholar 

  147. Mameli M, Bellone C, Brown MT, Luscher C. Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area. Nat Neurosci. 2011;14:414–6.

    Article  CAS  PubMed  Google Scholar 

  148. Bocklisch C, Pascoli V, Wong JC, House DR, Yvon C, de Roo M, et al. Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area. Science. 2013;341:1521–5.

    Article  CAS  PubMed  Google Scholar 

  149. Yang H, de Jong JW, Tak Y, Peck J, Bateup HS, Lammel S. Nucleus accumbens subnuclei regulate motivated behavior via direct inhibition and disinhibition of VTA dopamine subpopulations. Neuron. 2018;97:434–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Edwards NJ, Tejeda HA, Pignatelli M, Zhang S, McDevitt RA, Wu J, et al. Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior. Nat Neurosci. 2017;20:438.

    Article  CAS  PubMed  Google Scholar 

  151. Francis TC, Gantz SC, Moussawi K, Bonci A. Synaptic and intrinsic plasticity in the ventral tegmental area after chronic cocaine. Curr Opin Neurobiol. 2019;54:66–72.

    Article  CAS  PubMed  Google Scholar 

  152. Creed M, Ntamati NR, Chandra R, Lobo MK, Luscher C. Convergence of reinforcing and anhedonic cocaine effects in the ventral pallidum. Neuron. 2016;92:214–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Heinsbroek JA, Neuhofer DN, Griffin WC 3rd, Siegel GS, Bobadilla AC, Kupchik YM, et al. Loss of plasticity in the D2-accumbens pallidal pathway promotes cocaine seeking. J Neurosci. 2017;37:757–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Williams MJ, Adinoff B. The role of acetylcholine in cocaine addiction. Neuropsychopharmacology. 2008;33:1779–97.

    Article  CAS  PubMed  Google Scholar 

  155. Calabresi P, Centonze D, Gubellini P, Pisani A, Bernardi G. Acetylcholine-mediated modulation of striatal function. Trends Neurosci. 2000;23:120–6.

    Article  CAS  PubMed  Google Scholar 

  156. Apicella P. The role of the intrinsic cholinergic system of the striatum: what have we learned from TAN recordings in behaving animals? Neuroscience. 2017;360:81–94.

    Article  CAS  PubMed  Google Scholar 

  157. Lim SA, Kang UJ, McGehee DS. Striatal cholinergic interneuron regulation and circuit effects. Front Synaptic Neurosci. 2014;6:22.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Witten IB, Lin SC, Brodsky M, Prakash R, Diester I, Anikeeva P, et al. Cholinergic interneurons control local circuit activity and cocaine conditioning. Science. 2010;330:1677–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Lee J, Finkelstein J, Choi JY, Witten IB. Linking cholinergic interneurons, synaptic plasticity, and behavior during the extinction of a cocaine-context association. Neuron. 2016;90:1071–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Hikida T, Kaneko S, Isobe T, Kitabatake Y, Watanabe D, Pastan I, et al. Increased sensitivity to cocaine by cholinergic cell ablation in nucleus accumbens. Proc Natl Acad Sci USA. 2001;98:13351–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Consolo S, Caltavuturo C, Colli E, Recchia M, Di Chiara G. Different sensitivity of in vivo acetylcholine transmission to D1 receptor stimulation in shell and core of nucleus accumbens. Neuroscience. 1999;89:1209–17.

    Article  CAS  PubMed  Google Scholar 

  162. Mark GP, Hajnal A, Kinney AE, Keys AS. Self-administration of cocaine increases the release of acetylcholine to a greater extent than response-independent cocaine in the nucleus accumbens of rats. Psychopharmacology. 1999;143:47–53.

    Article  CAS  PubMed  Google Scholar 

  163. Berlanga ML, Olsen CM, Chen V, Ikegami A, Herring BE, Duvauchelle CL, et al. Cholinergic interneurons of the nucleus accumbens and dorsal striatum are activated by the self-administration of cocaine. Neuroscience. 2003;120:1149–56.

    Article  CAS  PubMed  Google Scholar 

  164. Lovinger DM. Neurotransmitter roles in synaptic modulation, plasticity and learning in the dorsal striatum. Neuropharmacology. 2010;58:951–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Francis TC, Yano H, Demarest TG, Shen H, Bonci A. High-frequency activation of nucleus accumbens D1-MSNs drives excitatory potentiation on D2-MSNs. Neuron. 2019;103:432–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Avena NM, Rada PV. Cholinergic modulation of food and drug satiety and withdrawal. Physiol Behav. 2012;106:332–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Eipper-Mains JE, Kiraly DD, Duff MO, Horowitz MJ, McManus CJ, Eipper BA, et al. Effects of cocaine and withdrawal on the mouse nucleus accumbens transcriptome. Genes Brain Behav. 2013;12:21–33.

    Article  CAS  PubMed  Google Scholar 

  168. Wilson JM, Carroll ME, Lac ST, DiStefano LM, Kish SJ. Choline acetyltransferase activity is reduced in rat nucleus accumbens after unlimited access to self-administration of cocaine. Neurosci Lett. 1994;180:29–32.

    Article  CAS  PubMed  Google Scholar 

  169. Ribeiro EA, Salery M, Scarpa JR, Calipari ES, Hamilton PJ, Ku SM, et al. Transcriptional and physiological adaptations in nucleus accumbens somatostatin interneurons that regulate behavioral responses to cocaine. Nat Commun. 2018;9:1–10.

    Article  Google Scholar 

  170. Selvakumar B, Campbell PW, Milovanovic M, Park DJ, West AR, Snyder SH, et al. AMPA receptor upregulation in the nucleus accumbens shell of cocaine-sensitized rats depends upon S-nitrosylation of stargazin. Neuropharmacology. 2014;77:28–38.

    Article  CAS  PubMed  Google Scholar 

  171. Selvakumar B, Jenkins MA, Hussain NK, Huganir RL, Traynelis SF, Snyder SH. S-nitrosylation of AMPA receptor GluA1 regulates phosphorylation, single-channel conductance, and endocytosis. Proc Natl Acad Sci USA. 2013;110:1077–82.

    Article  CAS  PubMed  Google Scholar 

  172. Smith AC, Kupchik YM, Scofield MD, Gipson CD, Wiggins A, Thomas CA, et al. Synaptic plasticity mediating cocaine relapse requires matrix metalloproteinases. Nat Neurosci. 2014;17:1655–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Smith ACW, Scofield MD, Heinsbroek JA, Gipson CD, Neuhofer D, Roberts-Wolfe DJ, et al. Accumbens nNOS interneurons regulate cocaine relapse. J Neurosci. 2017;37:742–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Winters BD, Kruger JM, Huang X, Gallaher ZR, Ishikawa M, Czaja K, et al. Cannabinoid receptor 1-expressing neurons in the nucleus accumbens. Proc Natl Acad Sci USA. 2012;109:E2717–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Dong Y, Green T, Saal D, Marie H, Neve R, Nestler EJ, et al. CREB modulates excitability of nucleus accumbens neurons. Nat Neurosci. 2006;9:475–7.

    Article  CAS  PubMed  Google Scholar 

  176. Mu P, Moyer JT, Ishikawa M, Zhang Y, Panksepp J, Sorg BA, et al. Exposure to cocaine dynamically regulates the intrinsic membrane excitability of nucleus accumbens neurons. J Neurosci. 2010;30:3689–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Ishikawa M, Mu P, Moyer JT, Wolf JA, Quock RM, Davies NM, et al. Homeostatic synapse-driven membrane plasticity in nucleus accumbens neurons. J Neurosci. 2009;29:5820–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Kourrich S, Calu DJ, Bonci A. Intrinsic plasticity: an emerging player in addiction. Nat Rev Neurosci. 2015;16:173–84.

    Article  CAS  PubMed  Google Scholar 

  179. Wang J, Ishikawa M, Yang Y, Otaka M, Kim JY, Gardner GR, et al. Cascades of homeostatic dysregulation promote incubation of cocaine craving. J Neurosci. 2018;38:4316–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Yu J, Yan Y, Li KL, Wang Y, Huang YH, Urban NN, et al. Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration. Proc Natl Acad Sci USA. 2017;114:E8750–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Bobadilla AC, Heinsbroek JA, Gipson CD, Griffin WC, Fowler CD, Kenny PJ, et al. Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior. Prog Brain Res. 2017;235:93–112.

    Article  PubMed  PubMed Central  Google Scholar 

  182. Bobadilla AC, Dereschewitz E, Vaccaro L, Heinsbroek JA, Scofield MD, Kalivas PW. Cocaine and sucrose rewards recruit different seeking ensembles in the nucleus accumbens core. Mol Psychiatry. 2020;25:3150–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Carelli RM, Ijames SG, Crumling AJ. Evidence that separate neural circuits in the nucleus accumbens encode cocaine versus “natural” (water and food) reward. J Neurosci. 2000;20:4255–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Cruz FC, Babin KR, Leao RM, Goldart EM, Bossert JM, Shaham Y, et al. Role of nucleus accumbens shell neuronal ensembles in context-induced reinstatement of cocaine-seeking. J Neurosci. 2014;34:7437–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Zhou Y, Zhu H, Liu Z, Chen X, Su X, Ma C, et al. A ventral CA1 to nucleus accumbens core engram circuit mediates conditioned place preference for cocaine. Nat Neurosci. 2019;22:1986–99.

    Article  CAS  PubMed  Google Scholar 

  186. Sjulson L, Peyrache A, Cumpelik A, Cassataro D, Buzsaki G. Cocaine place conditioning strengthens location-specific hippocampal coupling to the nucleus accumbens. Neuron. 2018;98:926–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Hebb DO. The organization of behavior: a neuropsychological theory. J. Wiley; New York: John Wiley and Sons, Inc.; 1949.

  188. Josselyn SA, Tonegawa S. Memory engrams: recalling the past and imagining the future. Science. 2020;367:1–14.

  189. Parrilla-Carrero J, Buchta WC, Goswamee P, Culver O, McKendrick G, Harlan B, et al. Restoration of Kv7 channel-mediated inhibition reduces cued-reinstatement of cocaine seeking. J Neurosci. 2018;38:4212–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Cruz FC, Koya E, Guez-Barber DH, Bossert JM, Lupica CR, Shaham Y, et al. New technologies for examining the role of neuronal ensembles in drug addiction and fear. Nat Rev Neurosci. 2013;14:743–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Whitaker LR, Hope BT. Chasing the addicted engram: identifying functional alterations in Fos-expressing neuronal ensembles that mediate drug-related learned behavior. Learn Mem. 2018;25:455–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. McDevitt DS, Jonik B, Graziane NM. Morphine differentially alters the synaptic and intrinsic properties of D1R- and D2R-expressing medium spiny neurons in the nucleus accumbens. Front Synaptic Neurosci. 2019;11:35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Hearing MC, Jedynak J, Ebner SR, Ingebretson A, Asp AJ, Fischer RA, et al. Reversal of morphine-induced cell-type-specific synaptic plasticity in the nucleus accumbens shell blocks reinstatement. Proc Natl Acad Sci USA. 2016;113:757–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Hamilton PJ, Burek DJ, Lombroso SI, Neve RL, Robison AJ, Nestler EJ, et al. Cell-type-specific epigenetic editing at the fosb gene controls susceptibility to social defeat stress. Neuropsychopharmacology. 2018;43:272–84.

    Article  CAS  PubMed  Google Scholar 

  195. Boudreau AC, Wolf ME. Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. J Neurosci. 2005;25:9144–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci. 2005;8:1481–9.

    Article  CAS  PubMed  Google Scholar 

  197. Pickens CL, Airavaara M, Theberge F, Fanous S, Hope BT, Shaham Y. Neurobiology of the incubation of drug craving. Trends Neurosci. 2011;34:411–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Venniro M, Caprioli D, Shaham Y. Animal models of drug relapse and craving: from drug priming-induced reinstatement to incubation of craving after voluntary abstinence. Prog Brain Res. 2016;224:25–52.

    Article  PubMed  Google Scholar 

  199. Joffe ME, Grueter CA, Grueter BA. Biological substrates of addiction. Wiley Interdiscip Rev Cogn Sci. 2014;5:151–71.

    Article  PubMed  PubMed Central  Google Scholar 

  200. Venniro M, Banks ML, Heilig M, Epstein DH, Shaham Y. Improving translation of animal models of addiction and relapse by reverse translation. Nat Rev Neurosci. 2020;21:625–43.

    Article  CAS  PubMed  Google Scholar 

  201. Richardson NR, Roberts DC. Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods. 1996;66:1–11.

    Article  CAS  PubMed  Google Scholar 

  202. Everitt BJ, Belin D, Economidou D, Pelloux Y, Dalley JW, Robbins TW. Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philos Trans R Soc Lond B Biol Sci. 2008;363:3125–35.

    Article  PubMed  PubMed Central  Google Scholar 

  203. O’Brien CP, Childress AR, Ehrman R, Robbins SJ. Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol. 1998;12:15–22.

    Article  PubMed  Google Scholar 

  204. Shalev U, Grimm JW, Shaham Y. Neurobiology of relapse to heroin and cocaine seeking: a review. Pharm Rev. 2002;54:1–42.

    Article  CAS  PubMed  Google Scholar 

  205. Shaham Y, Shalev U, Lu L, de Wit H, Stewart J. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology. 2003;168:3–20.

    Article  CAS  PubMed  Google Scholar 

  206. Markou A, Weiss F, Gold LH, Caine SB, Schulteis G, Koob GF. Animal models of drug craving. Psychopharmacology. 1993;112:163–82.

    Article  CAS  PubMed  Google Scholar 

  207. Grimm JW, Hope BT, Wise RA, Shaham Y. Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature. 2001;412:141–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Tran-Nguyen LT, Fuchs RA, Coffey GP, Baker DA, O’Dell LE, Neisewander JL. Time-dependent changes in cocaine-seeking behavior and extracellular dopamine levels in the amygdala during cocaine withdrawal. Neuropsychopharmacology. 1998;19:48–59.

    Article  CAS  PubMed  Google Scholar 

  209. Katz JL, Higgins ST. The validity of the reinstatement model of craving and relapse to drug use. Psychopharmacology. 2003;168:21–30.

    Article  CAS  PubMed  Google Scholar 

  210. Liao D, Hessler NA, Malinow R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature. 1995;375:400–4.

    Article  CAS  PubMed  Google Scholar 

  211. Isaac JT, Nicoll RA, Malenka RC. Evidence for silent synapses: implications for the expression of LTP. Neuron. 1995;15:427–34.

    Article  CAS  PubMed  Google Scholar 

  212. Bellone C, Luscher C. Drug-evoked plasticity: do addictive drugs reopen a critical period of postnatal synaptic development? Front Mol Neurosci. 2012;5:75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Preparation of this review was supported by NIH funds DA043826 (YHH), DA046346 (YHH), DA046491 (YHH), AA028145 (YHH), R01DA040620 (YD), R21DA047861 (YD), R37DA023206 (YD), and R21DA051010 (YD).

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    Alexander K. Zinsmaier & Yan Dong

  2. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    Yan Dong & Yanhua H. Huang

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Zinsmaier, A.K., Dong, Y. & Huang, Y.H. Cocaine-induced projection-specific and cell type-specific adaptations in the nucleus accumbens. Mol Psychiatry 27, 669–686 (2022). https://doi.org/10.1038/s41380-021-01112-2

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