Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction

Abstract

Abuse of and addiction to psychostimulants remains a challenging clinical issue, yet no effective pharmacotherapy is available. Trace amine associated receptor 1 (TAAR 1) is increasingly recognized as a novel drug target that participates in the modulation of drug abuse. This review analyzed existing preclinical evidence from electrophysiological, biochemical to behavioral aspects regarding the functional interactions between TAAR 1 and dopaminergic system. TAAR 1 knockout mice demonstrate increased sensitivity to dopaminergic activation while TAAR 1 agonists reduce the neurochemical effects of cocaine and amphetamines, attenuate abuse- and addiction-related behavioral effects of cocaine and methamphetamine. It is concluded that TAAR 1 activation functionally modulate the dopaminergic activity and TAAR 1 agonists appear to be promising pharmacotherapies against psychostimulant addiction.

In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1

“…Both selective TAAR1 partial agonists and selective TAAR1 full agonists reduced cocaine selfadministration and the reinstatement of drug-seeking behavior in rats (Pei et al, 2014 and decreased cocaine-mediated intracranial self-stimulation . Reductions of hyperlocomotion, self-administration, and reinstatement by TAAR1 partial agonism have also been reported for methamphetamine (Cotter et al, 2015;Jing and Li, 2015). These studies established TAAR1 as a promising target for therapeutics to treat substance use disorders, regardless of the TAAR1 binding properties of the abused substances themselves.…”

“…TAAR1 is thought to play a role in regulating the limbic network, reward circuits, cognitive processes, and mood states and has been proposed as a pharmacological target for the treatment of mental disorders (Wolinsky et al, 2007;Lindemann et al, 2008;Miller, 2011;Revel et al, 2013) and psychostimulant dependence (Di Cara et al, 2011;Pei et al, 2014;Cotter et al, 2015;Jing and Li, 2015). TAAR1 is stimulated by endogenous ligands, including b-phenylethylamine (b-PEA), p-tyramine, tryptamine, and 3-iodothyronamine (Scanlan et al, 2004;Zucchi et al, 2006).…”

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

“…Many psychoactive compounds bind to TAAR 1 (Bunzow et al, 2001;Simmler et al, 2013;Simmler et al, 2016), a potential target for the treatment of addiction (Cotter et al, 2015;Jing and Li, 2015;Pei et al, 2015). Psilocin, DMT, 4-OH-MET, and 5-MeO-AMT had low-micromolar affinity to TAAR 1rat .…”

Trace Amines and Their Receptors

“…Notwithstanding the difficulties, the last 15 years have seen a number of advances that have identified trace amines and their receptors as novel targets for the pharmacotherapy of various disorders, as well as being novel sites for environmental chemical interactions leading to behavioral ecology effects. Although a number of excellent reviews focusing on individual subareas of trace amine pharmacology, particularly in relation to TAAR1, have been published (Grandy, 2007;Sotnikova et al, 2008;Jing and Li, 2015;Lam et al, 552 2015;Liberles, 2015;Pei et al, 2016;Berry et al, 2017), a comprehensive review of all aspects of trace amine pharmacology is lacking. This article aims to provide such a comprehensive overview of the current state of the knowledge of trace amine systems throughout the body, in both vertebrates and invertebrates.…”