PMID- 21181122 OWN - NLM STAT- MEDLINE DCOM- 20110824 LR - 20220328 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 215 IP - 2 DP - 2011 May TI - Modulation of neuroplastic molecules in selected brain regions after chronic administration of the novel antidepressant agomelatine. PG - 267-75 LID - 10.1007/s00213-010-2129-8 [doi] AB - RATIONALE: Neuronal plasticity is associated with depression, probably as a result of modified expression of proteins important for cellular resiliency. It is therefore important to establish if and how antidepressant drugs may be able to regulate these mechanisms in order to achieve relevant clinical effects. OBJECTIVE: We investigated the effects of chronic treatment with agomelatine (an MT(1)/MT(2) receptor agonist and 5-HT(2C) receptor antagonist) on the brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF-2), and activity-regulated cytoskeleton-associated protein (Arc). METHODS: Animals were treated for 21 days with agomelatine, venlafaxine, or a vehicle and sacrificed 1 h (6 p.m.) or 16 h after the last injection (9 a.m.) to evaluate the messenger RNA (mRNA) and protein expression of these neuroplastic markers in the hippocampus and prefrontal cortex. RESULTS: Agomelatine, but not venlafaxine, produced major transcriptional changes in the hippocampus, where significant up-regulations of BDNF and FGF-2 were observed. Both drugs up-regulated the Arc transcription levels. No effects were observed in the prefrontal cortex. Instead, the levels of BDNF protein were elevated by agomelatine in both regions: the effects of the drug on mRNA levels in the hippocampus and cortex are different, while the effects on the protein seem to have the same cumulative result, suggesting different modulatory mechanisms in the two regions. CONCLUSIONS: Our data provide new information regarding the molecular mechanisms that contribute to the chronic effects of the new antidepressant agomelatine on brain function. The ability of agomelatine to modulate the expression of these neuroplastic molecules, which follows a circadian rhythm, may contribute to its antidepressant action. FAU - Calabrese, Francesca AU - Calabrese F AD - Center of Neuropharmacology, Department of Pharmacological Sciences, Universita degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy. FAU - Molteni, Raffaella AU - Molteni R FAU - Gabriel, Cecilia AU - Gabriel C FAU - Mocaer, Elisabeth AU - Mocaer E FAU - Racagni, Giorgio AU - Racagni G FAU - Riva, Marco A AU - Riva MA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101222 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Acetamides) RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclohexanols) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 137R1N49AD (agomelatine) RN - 7D7RX5A8MO (Venlafaxine Hydrochloride) SB - IM MH - Acetamides/*pharmacology MH - Animals MH - Antidepressive Agents/*pharmacology MH - Brain/anatomy & histology/*drug effects MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cyclohexanols/pharmacology MH - Cytosol/drug effects/metabolism MH - Fibroblast Growth Factor 2/genetics/metabolism MH - Gene Expression Regulation/*drug effects MH - Neuronal Plasticity/*drug effects/genetics MH - Rats MH - Rats, Sprague-Dawley MH - Synaptosomes/drug effects/metabolism MH - Time Factors MH - Venlafaxine Hydrochloride EDAT- 2010/12/25 06:00 MHDA- 2011/08/25 06:00 CRDT- 2010/12/25 06:00 PHST- 2010/08/24 00:00 [received] PHST- 2010/12/01 00:00 [accepted] PHST- 2010/12/25 06:00 [entrez] PHST- 2010/12/25 06:00 [pubmed] PHST- 2011/08/25 06:00 [medline] AID - 10.1007/s00213-010-2129-8 [doi] PST - ppublish SO - Psychopharmacology (Berl). 2011 May;215(2):267-75. doi: 10.1007/s00213-010-2129-8. Epub 2010 Dec 22.