Growing evidence suggests that the activation of the inflammatory/immune system contributes to depression pathogenesis, a hypothesis that might hold strong clinical implication. Indeed more than 30% of depressed patients fail to achieve remission, which poses the necessity to identify systems that may represent novel targets for medications. Accordingly, goal of this study was to evaluate the ability of the antidepressant agomelatine to modulate specific components of the immune response in the rat brain following an inflammatory challenge with lipopolysaccharide (LPS). To this aim, adult male rats were chronically treated with agomelatine before being acutely challenged with LPS 16 h after the last drug administration. Rats were sacrificed 2, 6, or 24h after the challenge and several components of the inflammatory response have been investigated by using real-time PCR or ELISA. We found that agomelatine significantly reduced the LPS-induced up-regulation of the pro-inflammatory cytokines interleukin-1β and interleukin-6 in the rat brain as well as at peripheral level. At central level, these effects are associated to the inhibition of NF-κB translocation as well as to alterations of mechanisms responsible for microglia activation. In addition, we found that agomelatine was also able to alter the expression of enzymes related to the kynurenine pathway that are thought to represent important mediators to inflammation-related depression. These data disclose novel properties that may contribute to the therapeutic effect of agomelatine providing evidence for a crucial role of specific components of the immune/inflammatory system in the antidepressant response and thereby in depression etiopathology.
Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine / R. Molteni, F. Macchi, C. Zecchillo, M. Dell'Agli, E. Colombo, F. Calabrese, G. Guidotti, G. Racagni, M.A. Riva. - In: EUROPEAN NEUROPSYCHOPHARMACOLOGY. - ISSN 0924-977X. - 23:11(2013 Nov), pp. 1645-1655.
|Titolo:||Modulation of the inflammatory response in rats chronically treated with the antidepressant agomelatine|
MOLTENI, RAFFAELLA (Primo)
MACCHI, FLAVIA (Secondo)
RIVA, MARCO ANDREA (Ultimo)
|Parole Chiave:||Depression ; Gene expression ; Hippocampus ; Lipopolysaccharide ; Microglia ; Tryptophan catabolism|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||nov-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.euroneuro.2013.03.008|
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