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Review
. 2022 Jan;27(1):220-229.
doi: 10.1038/s41380-021-01180-4. Epub 2021 Jun 11.

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment

Milky Kohno  1   2   3   4 , Laura E Dennis  5   6 , Holly McCready  5   6 , William F Hoffman  5   7   6   8   9
Affiliations
Review

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment

Milky Kohno et al. Mol Psychiatry. 2022 Jan.

Abstract

Dopamine system deficiencies and associated behavioral phenotypes may be a critical barrier to success in treating stimulant use disorders. Similarities in dopamine dysfunction between cocaine and methamphetamine use disorder but also key differences may impact treatment efficacy and outcome. This review will first compare the epidemiology of cocaine and methamphetamine use disorder. A detailed account of the pharmacokinetic and pharmacodynamic properties associated with each drug will then be discussed, with an emphasis on effects on the dopamine system and associated signaling pathways. Lastly, treatment results from pharmacological clinical trials will be summarized along with a more comprehensive review of the involvement of the trace amine-associated receptor on dopamine signaling dysfunction among stimulants and its potential as a therapeutic target.

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Conflict of interest statement

Conflict of Interest

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.. Mechanistic comparisons of methamphetamine and cocaine and the implications for treatment.
Similarities and differences between methamphetamine and cocaine on dopamine signaling may confer differences in treatment approaches.
See this image and copyright information in PMC

References

    1. World Drug Report 2020. (United Nations publication, Sales No. E.20.XI.6).
    1. Koob GF. Circuits, drugs, and drug addiction. Adv Pharmacol 1998; 42: 978–982. - PubMed
    1. Ashok AH, Mizuno Y, Volkow ND, Howes OD. Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine: A Systematic Review and Meta-analysis. JAMA Psychiatry 2017; 74(5): 511–519. - PMC - PubMed
    1. Proebstl L, Kamp F, Manz K, Krause D, Adorjan K, Pogarell O et al. Effects of stimulant drug use on the dopaminergic system: A systematic review and meta-analysis of in vivo neuroimaging studies. Eur Psychiatry 2019; 59: 15–24. - PubMed
    1. Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI et al. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol 2001; 60(6): 1181–1188. - PubMed

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