S18 Molecular neuropsychopharmacology [2] W´ ojcikowski, J., Golembiowska, K., Daniel, W.A., 2007, The regulation of liver cytochrome p450 by the brain dopaminergic system. Curr Drug Metab 8(6): 631–638. P.1.19 The galanin system in the human brain and relations with serotonin and noradrenaline neurons E. Le Ma¨ ıtre 1 ° , R. Diaz Heijtz 1 , M. Palkovits 2 , T. H¨ okfelt 1 . 1 Karolinska Institute, Dept of Neuroscience, Stockholm, Sweden; 2 Semmelweis University and the Hungarian Academy of Sciences, Neuromorphological and Neuroendocrine Research Laboratory Dept of Anatomy, Budapest, Hungary Purpose of the study: The objective of this project is to further analyse the functional significance of the neuropeptide galanin in mechanisms underlying mood control, with special focus on the human brain. Indeed, most of the work on the role of neuropeptides in mood regulation is based on experiments with rodents, and very little is known about the situation in humans. This analysis will be performed in the context of the established coexpression of galanin in the ascending noradrenaline (NA) and 5-hydroxytryptamine (5-HT) systems of the rat, projecting to cortical and hippocampal areas, most likely involved in mood regulation. Galanin is a 29 aminoacid peptide with three galanin receptors, GalR1, GalR2, GalR3, belonging to the superfamily of 7-transmembrane G-protein coupled receptors. Some studies have shown that the galanin system could be implicated in mood disorder: for instance, a transgenic mouse model overexpressing galanin presents a depressive phenotype [1]; moreover, a recent study has also shown that two small-molecules, blood-brain-barrier penetrating antagonists to GalR3 are antidepressant/anxiolytic in several rat tests [2]. In our experiments, we will study the localization of the galanin system in human brain sections, in particular locus coeruleus and the dorsal raphe nucleus, in order to test the hypothesis that this system is involved in depression. Methods used in the study: We have amplified, by reverse transcriptase-polymerase chain reaction (RT- PCR) and using specific primers, unique regions of galanin, GalR1, GalR3, Tryptophane Hydroxylase (TPH) and Tyrosine Hydroxylase (TH) from a human brain cDNA library. These amplified cDNA segments have then been extracted and subcloned, and plasmids have been linearized with appropriate restriction enzymes. On human brain sections, we have then performed in situ hybridization with antisense and sense riboprobes. Summary of results: We have shown that galanin and GalR3 mRNA are present in the locus coeruleus, overlapping with TH, a marker for the NA system. Moreover, only GalR3 mRNA is present in the dorsal raphe nucleus, in areas where TPH mRNA, marker of the 5-HT system, is present. We can also find galanin mRNA at the level of the dorsal raphe nucleus, but not coexisting in serotonin neurons. GalR1 mRNA is abundant in the dorsal periaqueductal grey (PAG) but not in the dorsal raphe nucleus. Conclusions and Perspectives: In the present study, we have defined the distribution of galanin, GalR1 and GalR3 in relation to TH in locus coeruleus and TPH in the dorsal raphe nucleus. We will now compare the mRNA expression of the galanin peptide and its receptors in depressed patients (suicide) in order to determine if differences exist. The results will hopefully provide a basis for a better understanding of involvement of the galanin system in depression and possibly of the underlying pathology. Reference(s) [1] Kuteeva, E., H¨ okfelt, T., ¨ Ogren, S.O., 2005, Behavioural characterisation of transgenic mice overexpressing galanin under the PDGF-B promoter. Neuropeptides 39(3): 299–304. [2] Swanson, C.J., Blackburn, T.P., Zhang, X., Zheng, K., Xu, Z.Q., H¨ okfelt, T., Wolinsky, T.D., Konkel, M.J., Chen, H., Zhong, H., Walker, M.W., Craig, D.A., Gerald, C.P., Branchek, T.A., 2005, Anxiolytic- and antidepressant-like profiles of the galanin-3 receptor (Gal3) antagonists SNAP 37889 and SNAP 398299. Proc Natl Acad Sci USA 102(48), 17489–17494. P.1.20 Impact of vagus nerve stimulation on monoaminergic neurons S. Manta 1 ° , J. Dong 2 , G. Debonnel 2 , P. Blier 1 . 1 University of Ottawa Institute of Mental Health Research, Mood disorders research unit, Ottawa, Canada; 2 McGill University, Psychiatry, Montr´ eal, Canada Purpose of the study: Vagus nerve stimulation (VNS) is a recent intervention in treatment-resistant depression, yet, the mechanism of action of this antidepressant effect is not fully elucidated. Serotoninergic (5-HT), noradrenergic (NE), and dopaminergic (DA) systems are involved in the pathophysiology of depression. Electrophysiological recordings in the rat brain have already shown that VNS increases the firing rate of NE neurons after one hour, and that of 5-HT neuron only after 14 days [1] but nothing was done concerning DA neurons. This study was aimed at: (1) elucidating the mechanism by which VNS enhances 5-HT neurotransmission, (2) characterizing