The Trace of Non-classical Biogenic Amines: A New Road to Addiction Recovery

Abstract

Stimulant abuse is prevalent according to recent global epidemiological studies. Research into treatment for problematic stimulant abuse has yet to find a suitable pharmacotherapeutic agent to assist with detoxification, withdrawal and relapse prevention. The newly discovered trace amine-associated receptor 1 (TAAR1) constitutes a novel receptor target for medication development with significant potential to treat the pathological changes produced by chronic drug exposure, especially stimulant abuse. Here, I briefly review evidence indicating that TAAR1 modulates the activity of the dopamine system and strongly influences the neurochemical and behavioral actions of psychomotor stimulants. The evidence discussed confirms the view that TAAR1 is a promising candidate receptor for the design of new effective addiction therapies. The Classical Direct ApproachThe classical biogenic amines have been under the spotlight in the fields of neuropharmacology and neuropsychiatry for the past 50 years. Historically, the search for treatments for psychopathological disorders such as depression, anxiety and schizophrenia has focused on the receptors, transporters and metabolic pathways for three catecholamines -dopamine (DA), norepinephrine and epinephrine-, histamine and serotonin, and to a lesser extent on amino acid transmitters and their receptors. Biogenic amines play a fundamental role in modulating a wide variety of physiological and behavioural processes, including autonomic function, hormone regulation and motor control, and are believed to contribute critically to emotional and cognitive function, neurotoxicity and mental disease [1][2][3]. The advent of drugs aimed at these classical targets to treat affective and psychotic disorders remains to this date the single most relevant advance in pharmacotherapy but the discovery of these drugs was serendipitous. It did not derive from the identification of the neuronal and circuitlevel alterations underlying psychiatric illness. This lack of mechanistic understanding hampered the progress and further development of therapeutic agents. An area in which development of pharmacological treatments has been particularly difficult is addiction and addictiverelated disorders, most notably addiction to cocaine and amphetaminetype substances. Stimulant addiction is widely recognized for its treatment challenges [4,5]. Although several forms of non-specific pharmacology are currently in use, including anti-depressants and antiepileptic drugs, there are no specific and proven medications that can be used to facilitate detoxification, enhance retention in psychotherapy and generally promote quicker recovery from chronic stimulant abuse.Changes in DA transmission are critical for understanding the acute and long-term effects of chronic stimulant exposure. The ability of cocaine-like drugs to maintain self-administration in rodents is correlated with their potency in inhibiting the dopamine transporter (DAT) [6]. Moreover, the self-reported "high" induced by stimulants in humans appears ...