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.