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.

  • Research Highlight
  • Published:

A non-human primate model of cocaine addiction: interpreting associations with increased vs. decreased dopamine function

Neuropsychopharmacology volume 48, pages 1419–1421 (2023)Cite this article

Subjects

Mesocorticolimbic dopamine transmission promotes reward pursuit. Based on these observations, it has been proposed that individual differences in dopamine signaling might affect susceptibility to reward-related disorders, particularly addictions. Unclear, however, is whether the relevant perturbation is an increase or a decrease. These opposing views are highlighted in a paper published in the current issue of Neuropsychopharmacology [1]. In a labor-intensive non-human primate (NHP) model, greater initial propensity to self-administer intravenous cocaine was associated with higher striatal dopamine D2/3 receptor (DRD2/3) availability, as measured with positron emission tomography (PET) and [11C]raclopride. Over the following weeks and months (up to 13 months), there was a progressive increase in high-dose cocaine self-administration (15 0.2 mg/kg injections available/day, 5 days/week) and a progressive decrease in DRD2/3 binding. The latter effect was partially reversed by a month-long regimen of continuous raclopride exposure (a DRD2/3 antagonist) suggesting that the alterations likely reflect compensatory responses to changing receptor stimulation.

These elegant findings replicate and extend the same group’s prior work where elevated DRD2/3 availability was associated with greater acquisition of cocaine self-administration at low doses (≤0.01 mg/kg) [2]. Despite this, they contrast with findings from the group’s first NHP PET studies [3, 4]. In this earlier work, higher cocaine self-administration was associated with lower DRD2/3 availability. One interpretation, the authors propose, is that the divergent associations reflect a sex difference. The first studies tested males [3, 4]; the more recent studies tested females [1, 2].

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: Potential dopamine-related pathways to substance use disorders.

References

  1. Allen MI, Duke AN, Nader SH, Adler-Neal A, Sai KKS, Reboussin BA, et al. PET imaging of dopamine transporters and D2/3 receptors in female monkeys: effects of chronic cocaine self-administration. Neuropsychopharmacology. 2023. https://doi.org/10.1038/s41386-023-01622-3.

  2. Nader MA, Nader SH, Czoty PW, Riddick NV, Gage HD, Gould RW, et al. Social dominance in female monkeys: dopamine receptor function and cocaine reinforcement. Biol Psychiatry. 2012;72:414–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, et al. Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci. 2002;5:169–74.

    Article  CAS  PubMed  Google Scholar 

  4. Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL, Buchheimer N, et al. PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys. Nat Neurosci. 2006;9:1050–6.

    Article  CAS  PubMed  Google Scholar 

  5. Jaworska N, Cox SML, Tippler M, Castellanos-Ryan N, Benkelfat C, Parent S, et al. Extra-striatal dopamine2/3 receptor availability in youth at-risk for addictions. Neuropsychopharmacology. 2020;45:1498–505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr. Yavin Shaham for feedback on an earlier version of this commentary and Dr. Marin Halut for assistance creating the figure.

Author information

Authors and Affiliations

  1. Department of Psychiatry, McGill University, Montreal, QC, H3A 1A1, Canada

    Marco Leyton

  2. Department of Psychology, McGill University, Montreal, QC, H3A 1B1, Canada

    Marco Leyton

  3. Department of Neurology & Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada

    Marco Leyton

  4. Integrated Program in Neuroscience, McGill University, Montreal, QC, H3A 1A1, Canada

    Marco Leyton & Maja Nikolic

  5. Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, H4B 1R6, Canada

    Marco Leyton

  6. Research Unit on Children’s Psychosocial Maladjustment, Université de Montréal, Montreal, QC, H3C 3J7, Canada

    Marco Leyton

Authors
  1. Marco Leyton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maja Nikolic
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ML wrote the commentary’s first draft with input and revisions from MN. MN designed the figure with input and revisions from ML. Both authors reviewed and approved the final version.

Corresponding author

Correspondence to Marco Leyton.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leyton, M., Nikolic, M. A non-human primate model of cocaine addiction: interpreting associations with increased vs. decreased dopamine function. Neuropsychopharmacol. 48, 1419–1421 (2023). https://doi.org/10.1038/s41386-023-01644-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41386-023-01644-x

Search

Advanced search

Quick links