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Electroretinographic modifications induced by agomelatine: a novel avenue to the understanding of the claimed antidepressant effect of the drug?

Authors Fornaro M, Bandini F, Cestari L, Cordano C, Ogliastro C, Albano C, De Berardis D, Martino M, Escelsior A, Rocchi G, Fornaro P, De Pasquale C

Received 4 March 2014

Accepted for publication 3 April 2014

Published 20 May 2014 Volume 2014:10 Pages 907—914


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Michele Fornaro,1 Fabio Bandini,2 Luca Cestari,3 Christian Cordano,4 Carla Ogliastro,4 Claudio Albano,4 Domenico De Berardis,5 Matteo Martino,6 Andrea Escelsior,6 Giulio Rocchi,6 Pantaleo Fornaro,6 Concetta De Pasquale1

1Department of Educative Science, University of Catania, Catania, Italy; 2Department of Neurology, San Paolo Hospital, Savona, Italy; 3Department of Ophthalmology, University of Pisa, Pisa, Italy; 4Department of Neurosciences, Ophthalmology and Genetics – Section of Neurology, University of Genoa, Genoa, Italy; 5National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital G. Mazzini, ASL 4, Teramo, Italy; 6Department of Neurosciences, Ophthalmology and Genetics – Section of Psychiatry, University of Genoa, Genoa, Italy

Background: Agomelatine, the first melatonergic antidepressant, has been postulated to enhance the dopaminergic activity at the central nervous system by 5-hydroxytryptamine receptor type 2C (5-HT2C) antagonism, yet the impact of melatonergic agonism on this pathway is unclear. Previous studies employing simplified, yet reliable, proxy (retinal) measures of the central nervous system dopaminergic activity, namely the standard electroretinogram (ERG) technique, suggested a reduction of the dopaminergic activity of the main ERG parameter, the b-wave, by pure melatonin, notably a hormone devoid of any antidepressant activity. Therefore, the antidepressant effects of the melatonergic antidepressant drug agomelatine should be reflected by a differential b-wave trend at ERG versus the effect exerted by pure melatonin, which was eventually found to be due to a contrasting effect on central dopaminergic transmission between the two drugs.
Objective and methods: The aim of the present preliminary ERG study carried out on healthy volunteers (n=23) receiving agomelatine was to explore the impact of this antidepressant drug on b-wave amplitude and latency of cones in daylight conditions using standard ERG.
Results: As postulated, agomelatine induced an enhancement of retinal dopaminergic activity, in contrast to what has been previously documented for melatonin.
Conclusion: Given the limits of this explorative study, especially the lack of a control group and that of a luminance response function to measure retinal sensitivity, further studies in clinical samples are recommended to allow more tenable conclusions about the potential role of ERG in discriminating between 5-HT antagonism and melatonergic (MT) agonism in relationship to the claimed antidepressant effect of agomelatine.

Keywords: electroretinogram, ERG, dopamine, 5-HT2C

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