• Lorenzo Di Cesare Mannelli, Elisa Vivoli, Alberto Salvicchi, Nicola Schiavone, Aleardo Koverech, Masa Messano, Raffaella Nicolai, Paola Benatti, Alessandro Bartolini, and Carla Ghelardini.
• Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. lorenzo.mannelli@unifi.it
• Psychopharmacology (Berl.). 2011 Nov 1; 218 (2): 347-56.

RationaleDepression may be associated with altered plasticity of the nervous system. The importance of neurotrophic factor levels is strongly suggested, and the neuronal-related family is extensively studied with respect to glial-derived one.ObjectivesAimed to contribute to the study of nervous plasticity modulation as therapeutical target in mood disorders, the role of the glial-derived factor artemin (ARTN) in depression and in the pharmacodynamics of the antidepressant and trophic compound acetyl-L: -carnitine (ALCAR) was evaluated.MethodsMale mice were treated with 100 mg kg(-1) ALCAR daily for 7 days; 0.6 μg/mouse ARTN was acutely injected intracerebroventricularly. Gene knockdown of ARTN and GDNF family receptor alpha (GFRalpha3) was obtained by oligonucleotide antisense strategy. The forced swimming test was performed to evaluate antidepressant-like effects.ResultsRepeated ALCAR administration increased ARTN levels in spinal cord, hippocampus, and prefrontal cortex. No modulatory effect was detected on BDNF and glial cell line-derived neutrotrophic factor (GDNF). ARTN, 30 min after administration, showed a dose-dependent antidepressant-like effect. ALCAR needed a 7-day treatment to reach a comparable effect; nevertheless, both substances were able to induce a phosphorylation of the GDNF family receptor Ret. A decrease of the free ARTN level by a specific ARTN antibody impaired the antidepressant-like effect of acute ARTN and repeated ALCAR. Gene knockdown of ARTN or, alternatively, of its receptor GFRalpha3 fully prevented ALCAR effectiveness.ConclusionsA mechanism for the antidepressant property of ALCAR is proposed, and the novelty of the possible role of ARTN in depression is suggested.

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