Mini Review ARTICLE

Front. Syst. Neurosci., 04 July 2011 |

Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons

Ada Ledonne1,2, Nicola Berretta2, Alessandro Davoli1,2, Giada Ricciardo Rizzo1,2, Giorgio Bernardi1,2 and Nicola Biagio Mercuri1,2*
  • 1 Università degli Studi di Roma “Tor Vergata,”, Rome, Italy
  • 2 Experimental Neurology Laboratory, Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Santa Lucia, Rome, Italy

Trace amines (TAs) are a class of endogenous compounds strictly related to classic monoamine neurotransmitters with regard to their structure, metabolism, and tissue distribution. Although the presence of TAs in mammalian brain has been recognized for decades, until recently they were considered to be by-products of amino acid metabolism or as “false” neurotransmitters. The discovery in 2001 of a new family of G-protein-coupled receptors (GPCRs), namely trace amines receptors, has re-ignited interest in TAs. In particular, two members of the family, trace amine receptor 1 (TA1) and trace amine receptor 2 (TA2), were shown to be highly sensitive to these endogenous compounds. Experimental evidence suggests that TAs modulate the activity of catecholaminergic neurons and that TA dysregulation may contribute to neuropsychiatric disorders, including schizophrenia, attention deficit hyperactivity disorder, depression and Parkinson’s disease, all of which are characterized by altered monoaminergic networks. Here we review recent data concerning the electrophysiological effects of TAs on the activity of mesencephalic dopaminergic neurons. In the context of recent data obtained with TA1 receptor knockout mice, we also discuss the mechanisms by which the activation of these receptors modulates the activity of these neurons. Three important new aspects of TAs action have recently emerged: (a) inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization. While the first two effects have been well documented in our laboratory, the direct activation of GIRK channels by TA1 receptors has been reported by others, but has not been seen in our laboratory (Geracitano et al., 2004). Further research is needed to address this point, and to further characterize the mechanism of action of TAs on dopaminergic neurons.

Keywords: dopaminergic neurons, tyramine, β-phenylethylamine, trace amine receptor 1, neuropsychiatric disorders

Citation: Ledonne A, Berretta N, Davoli A, Rizzo GR, Bernardi G and Mercuri NB (2011) Electrophysiological effects of trace amines on mesencephalic dopaminergic neurons. Front. Syst. Neurosci. 5:56. doi: 10.3389/fnsys.2011.00056

Received: 31 January 2011; Paper pending published: 27 March 2011;
Accepted: 16 June 2011; Published online: 04 July 2011.

Edited by:

Elizabeth Abercrombie, Rutgers Newark The State University of New Jersey, USA

Reviewed by:

Kuei Y. Tseng, Rosalind Franklin University of Medicine and Science, USA
James M. Tepper, Rutgers, The State University of New Jersey, USA

Copyright: © 2011 Ledonne, Berretta, Davoli, Rizzo, Bernardi and Mercuri. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Nicola Biagio Mercuri, Centro Europeo Ricerca sul Cervello, Via del Fosso di Fiorano 64 00143, Rome, Italy. e-mail: