Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

A large-scale c-Fos brain mapping study on extinction of cocaine-primed reinstatement

Neuropsychopharmacology (2024)Cite this article

Subjects

Abstract

Individuals with cocaine addiction can experience many craving episodes and subsequent relapses, which represents the main obstacle to recovery. Craving is often favored when abstinent individuals ingest a small dose of cocaine, encounter cues associated with drug use or are exposed to stressors. Using a cocaine-primed reinstatement model in rat, we recently showed that cocaine-conditioned interoceptive cues can be extinguished with repeated cocaine priming in the absence of drug reinforcement, a phenomenon we called extinction of cocaine priming. Here, we applied a large-scale c-Fos brain mapping approach following extinction of cocaine priming in male rats to identify brain regions implicated in processing the conditioned interoceptive stimuli of cocaine priming. We found that cocaine-primed reinstatement is associated with increased c-Fos expression in key brain regions (e.g., dorsal and ventral striatum, several prefrontal areas and insular cortex), while its extinction mostly disengages them. Moreover, while reinstatement behavior was correlated with insular and accumbal activation, extinction of cocaine priming implicated parts of the ventral pallidum, the mediodorsal thalamus and the median raphe. These brain patterns of activation and inhibition suggest that after repeated priming, interoceptive signals lose their conditioned discriminative properties and that action-outcome associations systems are mobilized in search for new contingencies, a brain state that may predispose to rapid relapse.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Extinction of cocaine priming.
Fig. 2: Brain-wide mapping of c-Fos expression following extinction of cocaine priming.
Fig. 3: Changes in c-Fos expression pattern following extinction of cocaine priming and correlations between c-Fos levels and active responses during the last Test.

Similar content being viewed by others

Data availability

All raw c-Fos data are available in the Supplementary files. Other data is available upon reasonable request to the corresponding authors.

References

  1. McLellan AT, Lewis DC, O’Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000;284:1689–95.

    Article  CAS  PubMed  Google Scholar 

  2. Sinha R. New findings on biological factors predicting addiction relapse vulnerability. Curr Psychiatry Rep. 2011;13:398–405.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Jaffe JH, Cascella NG, Kumor KM, Sherer MA. Cocaine-induced cocaine craving. Psychopharmacology. 1989;97:59–64.

    Article  CAS  PubMed  Google Scholar 

  4. Mahoney JJ 3rd, Kalechstein AD, De La Garza R 2nd, Newton TF. A qualitative and quantitative review of cocaine-induced craving: the phenomenon of priming. Prog Neuro Psychopharmacol Biol psychiatry. 2007;31:593–9.

    Article  CAS  Google Scholar 

  5. 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 

  6. Sinha R, Shaham Y, Heilig M. Translational and reverse translational research on the role of stress in drug craving and relapse. Psychopharmacology. 2011;218:69–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Courtney KE, Schacht JP, Hutchison K, Roche DJ, Ray LA. Neural substrates of cue reactivity: association with treatment outcomes and relapse. Addiction Biol. 2016;21:3–22.

    Article  Google Scholar 

  8. 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 

  9. de Wit H, Stewart J. Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology. 1981;75:134–43.

    Article  PubMed  Google Scholar 

  10. Epstein DH, Preston KL, Stewart J, Shaham Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology. 2006;189:1–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tunstall BJ, Kearns DN. Reinstatement in a cocaine versus food choice situation: reversal of preference between drug and non-drug rewards. Addiction Biol. 2014;19:838–48.

    Article  Google Scholar 

  12. Perry AN, Westenbroek C, Becker JB. The development of a preference for cocaine over food identifies individual rats with addiction-like behaviors. PloS One. 2013;8:e79465.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Leri F, Stewart J. Drug-induced reinstatement to heroin and cocaine seeking: a rodent model of relapse in polydrug use. Exp Clin Psychopharmacol. 2001;9:297–306.

    Article  CAS  PubMed  Google Scholar 

  14. Montanari C, Stendardo E, De Luca MT, Meringolo M, Contu L, Badiani A. Differential vulnerability to relapse into heroin versus cocaine-seeking as a function of setting. Psychopharmacology. 2015;232:2415–24.

    Article  CAS  PubMed  Google Scholar 

  15. Wang B, You ZB, Oleson EB, Cheer JF, Myal S, Wise RA. Conditioned contribution of peripheral cocaine actions to cocaine reward and cocaine-seeking. Neuropsychopharmacology. 2013;38:1763–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wise RA, Wang B, You ZB. Cocaine serves as a peripheral interoceptive conditioned stimulus for central glutamate and dopamine release. PloS One. 2008;3:e2846.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wise RA, Kiyatkin EA. Differentiating the rapid actions of cocaine. Nat Rev Neurosci. 2011;12:479–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wakabayashi KT, Kiyatkin EA. Critical role of peripheral drug actions in experience-dependent changes in nucleus accumbens glutamate release induced by intravenous cocaine. J Neurochem. 2014;128:672–85.

    Article  CAS  PubMed  Google Scholar 

  19. Lenoir M, Kiyatkin EA. Critical role of peripheral actions of intravenous nicotine in mediating its central effects. Neuropsychopharmacology. 2011;36:2125–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lenoir M, Kiyatkin EA. Intravenous nicotine injection induces rapid, experience-dependent sensitization of glutamate release in the ventral tegmental area and nucleus accumbens. J Neurochem. 2013;127:541–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lenoir M, Tang JS, Woods AS, Kiyatkin EA. Rapid sensitization of physiological, neuronal, and locomotor effects of nicotine: critical role of peripheral drug actions. J Neurosci. 2013;33:9937–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mihindou C, Vouillac C, Koob GF, Ahmed SH. Preclinical validation of a novel cocaine exposure therapy for relapse prevention. Biol Psychiatry. 2011;70:593–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Girardeau P, Navailles S, Durand A, Vouillac-Mendoza C, Guillem K, Ahmed SH. Relapse to cocaine use persists following extinction of drug-primed craving. Neuropharmacology. 2019;155:185–93.

    Article  CAS  PubMed  Google Scholar 

  24. Kalivas PW, McFarland K. Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology. 2003;168:44–56.

    Article  CAS  PubMed  Google Scholar 

  25. Kalivas PW, Volkow ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry. 2005;162:1403–13.

    Article  PubMed  Google Scholar 

  26. Farrell MR, Schoch H, Mahler SV. Modeling cocaine relapse in rodents: Behavioral considerations and circuit mechanisms. Prog Neuro Psychopharmacol Biol Psychiatry. 2018;87:33–47.

    Article  CAS  Google Scholar 

  27. Bossert JM, Marchant NJ, Calu DJ, Shaham Y. The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research. Psychopharmacology. 2013;229:453–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Capriles N, Rodaros D, Sorge RE, Stewart J. A role for the prefrontal cortex in stress- and cocaine-induced reinstatement of cocaine seeking in rats. Psychopharmacology. 2003;168:66–74.

    Article  CAS  PubMed  Google Scholar 

  29. Stefanik MT, Moussawi K, Kupchik YM, Smith KC, Miller RL, Huff ML, et al. Optogenetic inhibition of cocaine seeking in rats. Addiction Biol. 2013;18:50–3.

    Article  CAS  Google Scholar 

  30. Stefanik MT, Kupchik YM, Brown RM, Kalivas PW. Optogenetic evidence that pallidal projections, not nigral projections, from the nucleus accumbens core are necessary for reinstating cocaine seeking. J Neurosci. 2013;33:13654–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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 

  32. Navailles S, Guillem K, Vouillac-Mendoza C, Ahmed SH. Coordinated Recruitment of Cortical-Subcortical Circuits and Ascending Dopamine and Serotonin Neurons During Inhibitory Control of Cocaine Seeking in Rats. Cereb Cortex. 2015;25:3167–81.

    Article  PubMed  Google Scholar 

  33. Lenoir M, Navailles S, Vandaele Y, Vouillac-Mendoza C, Guillem K, Ahmed SH. Large-scale brain correlates of sweet versus cocaine reward in rats. Eur J Neurosci. 2023;57:423–39.

    Article  CAS  PubMed  Google Scholar 

  34. Lenoir M, Augier E, Vouillac C, Ahmed SH. A choice-based screening method for compulsive drug users in rats. Curr Protoc Neurosci. 2013;Chapter 9:Unit 9 44.

    PubMed  Google Scholar 

  35. Madsen HB, Ahmed SH. Drug versus sweet reward: greater attraction to and preference for sweet versus drug cues. Addiction Biol. 2015;20:433–44.

    Article  CAS  Google Scholar 

  36. Ahmed SH, Cador M. Dissociation of psychomotor sensitization from compulsive cocaine consumption. Neuropsychopharmacology. 2006;31:563–71.

    Article  CAS  PubMed  Google Scholar 

  37. Lenoir M, Ahmed SH. Heroin-induced reinstatement is specific to compulsive heroin use and dissociable from heroin reward and sensitization. Neuropsychopharmacology. 2007;32:616–24.

    Article  CAS  PubMed  Google Scholar 

  38. Kovacs KJ. c-Fos as a transcription factor: a stressful (re)view from a functional map. Neurochem Int. 1998;33:287–97.

    Article  CAS  PubMed  Google Scholar 

  39. Young ST, Porrino LJ, Iadarola MJ. Cocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors. Proc Natl Acad Sci USA. 1991;88:1291–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Martinez M, Phillips PJ, Herbert J. Adaptation in patterns of c-fos expression in the brain associated with exposure to either single or repeated social stress in male rats. Eur J Neurosci. 1998;10:20–33.

    Article  CAS  PubMed  Google Scholar 

  41. Mihindou C, Guillem K, Navailles S, Vouillac C, Ahmed SH. Discriminative inhibitory control of cocaine seeking involves the prelimbic prefrontal cortex. Biol Psychiatry. 2013;73:271–9.

    Article  CAS  PubMed  Google Scholar 

  42. Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc. 1995;57:289–300.

    Article  Google Scholar 

  43. Livneh Y, Andermann ML. Cellular activity in insular cortex across seconds to hours: Sensations and predictions of bodily states. Neuron. 2021;109:3576–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. McGregor MS, LaLumiere RT. Still a “hidden island”? The rodent insular cortex in drug seeking, reward, and risk. Neurosci Biobehav Rev. 2023;153:105334.

    Article  CAS  PubMed  Google Scholar 

  45. Zhou L, Pruitt C, Shin CB, Garcia AD, Zavala AR, See RE. Fos expression induced by cocaine-conditioned cues in male and female rats. Brain Struct Funct. 2014;219:1831–40.

    Article  CAS  PubMed  Google Scholar 

  46. Engeln M, Mitra S, Chandra R, Gyawali U, Fox ME, Dietz DM, et al. Sex-Specific Role for Egr3 in Nucleus Accumbens D2-Medium Spiny Neurons Following Long-Term Abstinence From Cocaine Self-administration. Biol Psychiatry. 2020;87:992–1000.

    Article  CAS  PubMed  Google Scholar 

  47. Walker QD, Ray R, Kuhn CM. Sex differences in neurochemical effects of dopaminergic drugs in rat striatum. Neuropsychopharmacology. 2006;31:1193–202.

    Article  CAS  PubMed  Google Scholar 

  48. Fuchs RA, Evans KA, Parker MP, See RE. Differential involvement of orbitofrontal cortex subregions in conditioned cue-induced and cocaine-primed reinstatement of cocaine seeking in rats. J Neurosci. 2004;24:6600–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tremblay L, Schultz W. Relative reward preference in primate orbitofrontal cortex. Nature. 1999;398:704–8.

    Article  CAS  PubMed  Google Scholar 

  50. Gabriele A, See RE. Lesions and reversible inactivation of the dorsolateral caudate-putamen impair cocaine-primed reinstatement to cocaine-seeking in rats. Brain Res. 2011;1417:27–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Saunders BT, Robinson TE. Individual variation in the motivational properties of cocaine. Neuropsychopharmacology. 2011;36:1668–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Khoo SY, Samaha AN. Metabotropic glutamate group II receptor activation in the ventrolateral dorsal striatum suppresses incentive motivation for cocaine in rats. Psychopharmacology. 2023;240:1247–60.

    Article  CAS  PubMed  Google Scholar 

  53. Robbe D. To move or to sense? Incorporating somatosensory representation into striatal functions. Curr Opin Neurobiol. 2018;52:123–30.

    Article  CAS  PubMed  Google Scholar 

  54. Vandaele Y, Mahajan NR, Ottenheimer DJ, Richard JM, Mysore SP, Janak PH. Distinct recruitment of dorsomedial and dorsolateral striatum erodes with extended training. eLife. 2019;8:e49536.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Vandaele Y, Ottenheimer DJ, Janak PH. Dorsomedial Striatal Activity Tracks Completion of Behavioral Sequences in Rats. eNeuro. 2021;8:ENEURO.0279–21.2021.

    Article  PubMed  Google Scholar 

  56. Pascoli V, Hiver A, Van Zessen R, Loureiro M, Achargui R, Harada M, et al. Stochastic synaptic plasticity underlying compulsion in a model of addiction. Nature. 2018;564:366–71.

    Article  CAS  PubMed  Google Scholar 

  57. Harada M, Pascoli V, Hiver A, Flakowski J, Luscher C. Corticostriatal Activity Driving Compulsive Reward Seeking. Biol Psychiatry. 2021;90:808–18.

    Article  PubMed  Google Scholar 

  58. Ahmari SE, Spellman T, Douglass NL, Kheirbek MA, Simpson HB, Deisseroth K, et al. Repeated cortico-striatal stimulation generates persistent OCD-like behavior. Science. 2013;340:1234–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Cornish JL, Duffy P, Kalivas PW. A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience. 1999;93:1359–67.

    Article  CAS  PubMed  Google Scholar 

  60. Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, et al. Input-specific control of reward and aversion in the ventral tegmental area. Nature. 2012;491:212–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lammel S, Ion DI, Roeper J, Malenka RC. Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron. 2011;70:855–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Verharen JPH, Zhu Y, Lammel S. Aversion hot spots in the dopamine system. Curr Opin Neurobiol. 2020;64:46–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Badrinarayan A, Wescott SA, Vander Weele CM, Saunders BT, Couturier BE, Maren S, et al. Aversive stimuli differentially modulate real-time dopamine transmission dynamics within the nucleus accumbens core and shell. J Neurosci. 2012;32:15779–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Mantsch JR, Goeders NE. Generalization of a restraint-induced discriminative stimulus to cocaine in rats. Psychopharmacology. 1998;135:423–6.

    Article  CAS  PubMed  Google Scholar 

  65. Augier E, Vouillac C, Ahmed SH. Diazepam promotes choice of abstinence in cocaine self-administering rats. Addiction Biol. 2012;17:378–91.

    Article  CAS  Google Scholar 

  66. Naqvi NH, Gaznick N, Tranel D, Bechara A. The insula: a critical neural substrate for craving and drug seeking under conflict and risk. Ann N Y Acad Sci. 2014;1316:53–70.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Contreras M, Ceric F, Torrealba F. Inactivation of the interoceptive insula disrupts drug craving and malaise induced by lithium. Science. 2007;318:655–8.

    Article  CAS  PubMed  Google Scholar 

  68. Gogolla N. The insular cortex. Curr Biol. 2017;27:R580–R86.

    Article  CAS  PubMed  Google Scholar 

  69. Cosme CV, Gutman AL, LaLumiere RT. The Dorsal Agranular Insular Cortex Regulates the Cued Reinstatement of Cocaine-Seeking, but not Food-Seeking, Behavior in Rats. Neuropsychopharmacology. 2015;40:2425–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Arguello AA, Wang R, Lyons CM, Higginbotham JA, Hodges MA, Fuchs RA. Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats. Psychopharmacology. 2017;234:2431–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rotge JY, Cocker PJ, Daniel ML, Belin-Rauscent A, Everitt BJ, Belin D. Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula. Psychopharmacology. 2017;234:1623–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Gehrlach DA, Weiand C, Gaitanos TN, Cho E, Klein AS, Hennrich AA, et al. A whole-brain connectivity map of mouse insular cortex. eLife. 2020;9:e55585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Allen GV, Saper CB, Hurley KM, Cechetto DF. Organization of visceral and limbic connections in the insular cortex of the rat. J Comp Neurol. 1991;311:1–16.

    Article  CAS  PubMed  Google Scholar 

  74. Parnaudeau S, Taylor K, Bolkan SS, Ward RD, Balsam PD, Kellendonk C. Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior. Biol Psychiatry. 2015;77:445–53.

    Article  PubMed  Google Scholar 

  75. Wolff M, Alcaraz F, Marchand AR, Coutureau E. Functional heterogeneity of the limbic thalamus: From hippocampal to cortical functions. Neurosci Biobehav Rev. 2015;54:120–30.

    Article  PubMed  Google Scholar 

  76. Haaranen M, Scuppa G, Tambalo S, Jarvi V, Bertozzi SM, Armirotti A, et al. Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats. Transl Psychiatry. 2020;10:150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Reynolds SM, Zahm DS. Specificity in the projections of prefrontal and insular cortex to ventral striatopallidum and the extended amygdala. J Neurosci. 2005;25:11757–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Parnaudeau S, O’Neill PK, Bolkan SS, Ward RD, Abbas AI, Roth BL, et al. Inhibition of mediodorsal thalamus disrupts thalamofrontal connectivity and cognition. Neuron. 2013;77:1151–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Root DH, Ma S, Barker DJ, Megehee L, Striano BM, Ralston CM, et al. Differential roles of ventral pallidum subregions during cocaine self-administration behaviors. J Comp Neurol. 2013;521:558–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Root DH, Melendez RI, Zaborszky L, Napier TC. The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors. Prog Neurobiol. 2015;130:29–70.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Engeln M, Fox ME, Chandra R, Choi EY, Nam H, Qadir H, et al. Transcriptome profiling of the ventral pallidum reveals a role for pallido-thalamic neurons in cocaine reward. Mol Psychiatry. 2022;27:3980–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Vertes RP, Fortin WJ, Crane AM. Projections of the median raphe nucleus in the rat. J Comp Neurol. 1999;407:555–82.

    Article  CAS  PubMed  Google Scholar 

  83. Szonyi A, Zicho K, Barth AM, Gonczi RT, Schlingloff D, Torok B, et al. Median raphe controls acquisition of negative experience in the mouse. Science. 2019;366:eaay8746.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Eric Wattelet for administrative assistance. We also thank Sandra Dovero, Evelyne Doudnikoff, and Matthieu Bastide for technical advice, and Etienne Gontier from the Bordeaux Imaging Center (BIC) for giving us access to his laboratory facility for brain perfusion.

Funding

This research was supported by funding from the Centre National de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (ANR- 2010-BLAN-1404-01), the Université de Bordeaux and the Conseil Regional d’Aquitaine (CRA11004375/11004699). 

Author information

Author notes

  1. These authors contributed equally: Magalie Lenoir, Michel Engeln.

Authors and Affiliations

  1. Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France

    Magalie Lenoir, Michel Engeln & Serge H. Ahmed

  2. Thales, 33700, Mérignac, France

    Sylvia Navailles

  3. Univ. Bordeaux, UFR des Sciences Odontologiques, Bordeaux, France

    Paul Girardeau

Authors
  1. Magalie Lenoir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michel Engeln
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sylvia Navailles
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul Girardeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Serge H. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SHA conceived the project. SN, PG and SHA designed the experiments. SN, PG performed the experiments and collected the experimental data. ML, ME analyzed the data. ML and ME wrote the first draft of the paper. ML, ME and SHA revised and edited the paper. All authors reviewed content and approved the final version of the manuscript.

Corresponding authors

Correspondence to Magalie Lenoir or Michel Engeln.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lenoir, M., Engeln, M., Navailles, S. et al. A large-scale c-Fos brain mapping study on extinction of cocaine-primed reinstatement. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01867-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41386-024-01867-6

Search

Advanced search

Quick links