Trace Amine-associated Receptor 1 and Drug Abuse

Overview

Journal Adv Pharmacol

Specialty Pharmacology

Date 2022 Mar 28

PMID 35341572

Authors

Ruyan Wu

Jianfeng Liu

Jun-Xu Li

Affiliations

Soon will be listed here.

Abstract

Trace amine-associated receptor 1 (TAAR1) is the best characterized receptor selectively activated by trace amines. It is broadly expressed in the monoaminergic system in the brain including ventral tegmental area (VTA), nucleus accumbens (NAc), dorsal raphe (DR) and substantial nigra (SN). Extensive studies have suggested that TAAR1 plays an important role in the modulation of monoaminergic system, especially dopamine (DA) transmission which may underlie the mechanisms by which TAAR1 interventions affect drug abuse-like behaviors. TAAR1 activation inhibits the rewarding and reinforcing effects of drugs from different classes including psychostimulants, opioid and alcohol as well as drug-induced increase in DA accumulation. The mechanisms of TAAR1's function in mediating drug abuse-like behaviors are not clear. However, it is hypothesized that TAAR1 interaction with DA transporter (DAT) and dopamine D2 receptor (D2) and the subsequent modulation of cellular cascades may contribute to the effects of TAAR1 in regulating drug abuse. Further studies are needed to investigate the role of TAAR1 in other drugs of abuse-related behaviors and its safety and efficacy for prolonged medications. Together, TAAR1 inhibits drug-induced DA transmission and drug abuse-related behaviors. Therefore, TAAR1 may be a promising therapeutic target for the treatment of drug addiction.

Citing Articles

Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders.

Kuvarzin S, Sukhanov I, Onokhin K, Zakharov K, Gainetdinov R Biomedicines. 2023; 11(7).

PMID: 37509616 PMC: 10377193. DOI: 10.3390/biomedicines11071977.

Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet.

Apryatin S, Zhukov I, Zolotoverkhaya E, Kuvarzin S, Khunagov T, Ushmugina S Neurol Int. 2023; 15(1):339-351.

PMID: 36976665 PMC: 10052549. DOI: 10.3390/neurolint15010022.

References

Lindemann L, Meyer C, Jeanneau K, Bradaia A, Ozmen L, Bluethmann H . Trace amine-associated receptor 1 modulates dopaminergic activity. J Pharmacol Exp Ther. 2007; 324(3):948-56. DOI: 10.1124/jpet.107.132647. View

Mansvelder H, Keath J, McGehee D . Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron. 2002; 33(6):905-19. DOI: 10.1016/s0896-6273(02)00625-6. View

Boulton A . Letter: Amines and theories in psychiatry. Lancet. 1974; 2(7871):52-3. DOI: 10.1016/s0140-6736(74)91390-7. View

Sukhanov I, Caffino L, Efimova E, Espinoza S, Sotnikova T, Cervo L . Increased context-dependent conditioning to amphetamine in mice lacking TAAR1. Pharmacol Res. 2015; 103:206-14. DOI: 10.1016/j.phrs.2015.11.002. View

Asif-Malik A, Hoener M, Canales J . Interaction Between the Trace Amine-Associated Receptor 1 and the Dopamine D Receptor Controls Cocaine's Neurochemical Actions. Sci Rep. 2017; 7(1):13901. PMC: 5655641. DOI: 10.1038/s41598-017-14472-z. View

Koblan K, Kent J, Hopkins S, Krystal J, Cheng H, Goldman R . A Non-D2-Receptor-Binding Drug for the Treatment of Schizophrenia. N Engl J Med. 2020; 382(16):1497-1506. DOI: 10.1056/NEJMoa1911772. View

Revel F, Meyer C, Bradaia A, Jeanneau K, Calcagno E, Andre C . Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine. Neuropsychopharmacology. 2012; 37(12):2580-92. PMC: 3473323. DOI: 10.1038/npp.2012.109. View

Wainscott D, Little S, Yin T, Tu Y, Rocco V, He J . Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1. J Pharmacol Exp Ther. 2006; 320(1):475-85. DOI: 10.1124/jpet.106.112532. View

Wu R, Liu J, Wang K, Huang Y, Zhang Y, Li J . Effects of a trace amine-associated receptor 1 agonist RO 5263397 on ethanol-induced behavioral sensitization. Behav Brain Res. 2020; 390:112641. PMC: 7286772. DOI: 10.1016/j.bbr.2020.112641. View

10.

Wolinsky T, Swanson C, Smith K, Zhong H, Borowsky B, Seeman P . The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav. 2007; 6(7):628-39. DOI: 10.1111/j.1601-183X.2006.00292.x. View

11.

Liu J, Johnson B, Wu R, Seaman Jr R, Vu J, Zhu Q . TAAR1 agonists attenuate extended-access cocaine self-administration and yohimbine-induced reinstatement of cocaine-seeking. Br J Pharmacol. 2020; 177(15):3403-3414. PMC: 7348092. DOI: 10.1111/bph.15061. View

12.

Wheeler D, Underhill S, Stolz D, Murdoch G, Thiels E, Romero G . Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine. Proc Natl Acad Sci U S A. 2015; 112(51):E7138-47. PMC: 4697400. DOI: 10.1073/pnas.1511670112. View

13.

Simmler L, Buchy D, Chaboz S, Hoener M, Liechti M . In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1. J Pharmacol Exp Ther. 2016; 357(1):134-44. DOI: 10.1124/jpet.115.229765. View

14.

Leo D, Mus L, Espinoza S, Hoener M, Sotnikova T, Gainetdinov R . Taar1-mediated modulation of presynaptic dopaminergic neurotransmission: role of D2 dopamine autoreceptors. Neuropharmacology. 2014; 81:283-91. DOI: 10.1016/j.neuropharm.2014.02.007. View

15.

Xie Z, Westmoreland S, Bahn M, Chen G, Yang H, Vallender E . Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro. J Pharmacol Exp Ther. 2007; 321(1):116-27. DOI: 10.1124/jpet.106.116863. View

16.

Bunzow J, Sonders M, Arttamangkul S, Harrison L, Zhang G, Quigley D . 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):1181-8. DOI: 10.1124/mol.60.6.1181. View

17.

Reed C, Baba H, Zhu Z, Erk J, Mootz J, Varra N . A Spontaneous Mutation in Impacts Methamphetamine-Related Traits Exclusively in DBA/2 Mice from a Single Vendor. Front Pharmacol. 2018; 8():993. PMC: 5786530. DOI: 10.3389/fphar.2017.00993. View

18.

Lindemann L, Ebeling M, Kratochwil N, Bunzow J, Grandy D, Hoener M . Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics. 2005; 85(3):372-85. DOI: 10.1016/j.ygeno.2004.11.010. View

19.

Sotnikova T, Beaulieu J, Espinoza S, Masri B, Zhang X, Salahpour A . The dopamine metabolite 3-methoxytyramine is a neuromodulator. PLoS One. 2010; 5(10):e13452. PMC: 2956650. DOI: 10.1371/journal.pone.0013452. View

20.

Sukhanov I, Dorofeikova M, Dolgorukova A, Dorotenko A, Gainetdinov R . Trace Amine-Associated Receptor 1 Modulates the Locomotor and Sensitization Effects of Nicotine. Front Pharmacol. 2018; 9:329. PMC: 5898227. DOI: 10.3389/fphar.2018.00329. View