title: Differential effects of fluoxetine and venlafaxine on memory recognition: possible mechanisms of action.
abstract: Serotonin-specific reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are antidepressant drugs commonly used to treat a wide spectrum of mood disorders (Wong and Licinio, 2001). Although they have been clinically used for more than 50 years, the molecular and cellular basis for the action of SSRIs and SNRIs is not clear. Considering that the changes in gene expression involved in the action of antidepressant drugs on memory have not been identified, in this study we investigated the impact of chronic treatment with a SSRI (fluoxetine) and a SNRI (venlafaxine) on the mRNA expression of genes related to memory cascade in the mouse hippocampus, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), nitric oxide synthase 1 (NOS1), neurotrophic tyrosine kinase receptor type 2 (TrKB), mitogen-activated protein kinases (MAPK/ERK) and serotonin transporter (SERT). Animals treated with fluoxetine 10 mg/Kg/day for 28 days showed a significant decrease in the percentage of time spent in the novel object recognition test (p≤0.005) and induced MAPK1/ERK2 down-regulation (p=0.005). Our results suggest that the effect on cognition could probably be explained by fluoxetine interference in the MAPK/ERK memory pathway. In contrast, chronic treatment with venlafaxine did not reduce MAPK1/ERK2 expression, suggesting that MAPK1/ERK2 down-regulation is not a common effect of all antidepressant drugs. Further studies are needed to examine the effect of chronic fluoxetine treatment on the ERK-CREB system, and to determine whether there is a causal relationship between the disruption of the ERK-CREB system and the effect of this antidepressant on memory performance.
authors.affiliation: Cátedra de Fisiología Humana, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU, Córdoba, Argentina. vcarlini@live.com.ar
authors.forename: Valeria Paola
authors.initials: VP
authors.lastname: Carlini
authors.forename: María Belén
authors.initials: MB
authors.lastname: Poretti
authors.forename: Mathias
authors.initials: M
authors.lastname: Rask-Andersen
authors.forename: Rohit A
authors.initials: RA
authors.lastname: Chavan
authors.forename: Marina F
authors.initials: MF
authors.lastname: Ponzio
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Sawant
authors.forename: Susana Rubiales
authors.initials: SR
authors.lastname: de Barioglio
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
authors.forename: Marta Fiol
authors.initials: MF
authors.lastname: de Cuneo
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D051379:Mice; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D005473:Fluoxetine; D052248:Nitric Oxide Synthase Type I; D020813:Receptor, trkB; D018091:Receptors, AMPA; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride