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Abstract #1226

Effect of the Novel Anti-Depressant Agomelatine Determined by Pharmacological MRI in the Rat.

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.