Karen Elizabeth Davies1, Inna V. Linnik1, Shane Mckie2, Jennifer A. Stark3, Simon Luckman3, Laure Sequin4, Elisabeth Mocaer4, Mark Millan4, Bill Deakin2, Steve R. Williams1
1Imaging Science & Biomedical Engineering, University of Manchester, Manchester, United Kingdom; 2Neuroscience and Psychiatry Unit, University of Manchester, Manchester, United Kingdom; 3Faculty of Life Science, University of Manchester, Manchester, United Kingdom; 4Institut de Recherches Internationales, Servier, Courbevoie, France
phMRI was used to determine brain areas activated by the novel anti-depressant agomelatine at 3 doses. T2*-weighted GE images were acquired continuously before and after injection of agomelatine or vehicle in isoflurane-anaesthetized rats. A pseudoblock analysis was performed in SPM5, revealing significant areas of activation and deactivation including cortical, hippocampal and caudate regions. There was a marked effect of dose with more brain areas, more total voxels and higher Z-scores at a dose of 20mg/kg compared to either 10 or 40mg/kg. Agomelatine acts at both melatonin and serotonin receptors and both receptors are likely to be involved in these responses.