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Original Article

Trace Amines Depress GABA_B Response in Dopaminergic Neurons by Inhibiting G--Gated Inwardly Rectifying Potassium Channels

Experimental Neurology Laboratory, S. Lucia Foundation Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy; and University of Rome "Tor Vergata", Rome, Italy

Abstract

Trace amines (TAs) are present in the central nervous system in which they up-regulate catecholamine release and are implicated in the pathogenesis of addiction, attention-deficit/hyper-activity disorder, Parkinson's disease, and schizophrenia. By using intracellular and patch-clamp recordings from dopaminergic cells in the rat midbrain slices, we report a depressant postsynaptic action of two TAs, -phenylethylamine (-PEA) and tyramine (TYR) on the GABA_B-mediated slow inhibitory postsynaptic potential and baclofen-activated outward currents. -PEA and TYR activated G-proteins, interfering with the coupling between GABA_B receptors and G--gated inwardly rectifying potassium channels. This is the first demonstration that -PEA and TYR depress inhibitory synaptic potentials in neurons of the central nervous system, supporting their emerging role as neuromodulators.

Address correspondence to: Dr. Nicola Biagio Mercuri, Department of Experimental Neurology, S. Lucia Foundation I.R.C.C.S., Via Ardeatina 306, 00179 Rome, Italy. E-mail: mercurin{at}med.uniroma2.it

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