THE TRACE AMINE PHENYLETHYLAMINE: ADHD AND COCAINE ABUSE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The trace amine phenylethylamine (PEA) is implicated in substance abuse, ADHD, depression, schizophrenia and others, but its physiological and pharmacological roles are poorly understood. Exogenous PEA regulates dopamine release via the dopamine (DA) transporter (DAT), but direct evidence for PEA transport has not been reported. We investigated PEA transport by the human DAT and norepinephrine transporter (NET) and whether psychostimulant drugs and medications affect PEA transport. Results: (3H)PEA affinities for the DAT and NET were similar ((3H)PEA: Km: 724 nM; (3H)DA: 797 nM), but (3H)PEA transport capacity was lower. (3H)PEA affinity (695 nM) was lower than (3H)NE affinity (478 nM) at the NET. Of ADHD medications, methylphenidate was more potent in blocking DAT transport of (3H)PEA than (3H)DA, whereas (d)-amphetamine was less potent. Psychostimulant drugs blocked (3H)PEA and (3H)DA transport but cocaine congeners were 3-6 times more potent in blocking (3H)PEA than (3H)DA transport. These contrasting affinities may reflect different binding domains of transporter substrates or conformational changes of the DAT. Discussion: PEA levels conceivably are modulated by ADHD medications and psychostimulant drugs of abuse. As a transport substrate and an agonist at the trace amine receptor1, PEA may contribute to neuropathology, to pharmacological effects of psychostimulant drugs of abuse and to the therapeutic efficacy of medications that target monoamine transporters.