Abstract
Trace amine-associated receptor 1 is one of the best-characterized receptors of trace amines. Growing evidence shows that TAAR1 negatively regulates the monoaminergic activity, including dopamine transmission in the mesocorticolimbic system. Neurochemical assays demonstrated that selective TAAR1 full and partial agonists were effective to prevent psychostimulants-induced dopamine transmission in vitro and in vivo. In the last decade, many preclinical models of psychostimulant addiction such as drug-induced behavioral sensitization, drug-induced conditioned place preference, drug self-administration, drug discrimination, and relapse models were used to assess the effects of TAAR1 agonists on psychostimulants’ behavioral effects. In general, activation of TAAR1 attenuated while knockout of TAAR1 potentiated psychostimulant abuse-related behaviors. Here, we review the advances in TAAR1 and its agonists in modulating psychostimulant addiction. We discuss the similarities and differences between the neurochemical and behavioral effects of TAAR1 full and partial agonists. We also discuss several concerns including the abuse liability, sleep reduction, and species-dependent effects that might affect the successful translation of TAAR1 agonists from preclinical studies to clinical application. In conclusion, although further investigations are in need to address certain concerns and the underlying neural mechanisms, TAAR1 agonists appear to be a promising pharmacotherapy to treat psychostimulant addiction and prevent relapse.
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This work was funded by the National Institutes of Health National Institute on Drug Abuse [Grants R21DA040777 and R01DA047967]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Liu, J., Wu, R. & Li, JX. TAAR1 and Psychostimulant Addiction. Cell Mol Neurobiol 40, 229–238 (2020). https://doi.org/10.1007/s10571-020-00792-8
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DOI: https://doi.org/10.1007/s10571-020-00792-8