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. 2014 May 20:10:907-14.
doi: 10.2147/NDT.S63459. eCollection 2014.

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

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 Pasquale  1
Affiliations

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

Michele Fornaro et al. Neuropsychiatr Dis Treat. .

Abstract

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: 5-HT2C; ERG; dopamine; electroretinogram.

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Figures

Figure 1
Figure 1
The a-wave of the electroretinogram reflects the activity of photoreceptors; the b-wave indicates the activity of the amacrine, horizontal, bipolar, and Müller cells. Implicit time refers to the time occurring between the initiation of the light stimulation (flash) and the peak of a- and b-waves. The a-wave amplitude was measured from baseline to a-wave trough; the b-wave amplitude was measured from a-wave trough to b-wave peak.
Figure 2
Figure 2
Flowchart of study procedures. Abbreviation: ERG, electroretinogram.
See this image and copyright information in PMC

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