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Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and 8 F-fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, P

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., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)