4.8 Review

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

期刊

MOLECULAR PSYCHIATRY
卷 27, 期 1, 页码 220-229

出版社

SPRINGERNATURE
DOI: 10.1038/s41380-021-01180-4

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资金

  1. Department of Veterans Affairs Clinical Sciences Research and Development Merit Review Program [I01 CX001558-01A1]
  2. Department of Justice [2010-DD-BX-0517]
  3. Oregon Clinical and Translational Research Institute from the National Center for Research Resources, a component of the National Institutes of Health [1 UL1 RR024140 01]
  4. National Institute of Health Roadmap for Medical Research [1 UL1 RR024140 01]
  5. National Institute on Alcohol Abuse and Alcoholism [R21 AA020039]
  6. Department of Veterans Affairs Clinical Sciences Research and Development Career Development [CX001790]
  7. Oregon Health & Science University Collins Medical Trust [APSYC0249]
  8. Medical Research Foundation of Oregon [APSYC0250]
  9. Center for Women's Health Circle of Giving [GPSYC0287A]
  10. National Institute on Drug Abuse [P50DA018165, R21 DA047602-01A1]

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This review compares the epidemiology of cocaine and methamphetamine use disorder, discusses the effects of drugs on the dopamine system, and summarizes treatment results from pharmacological clinical trials.
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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