Differential effects of fluoxetine and venlafaxine on memory recognition: possible mechanisms of action. 2012

Valeria Paola Carlini, and María Belén Poretti, and Mathias Rask-Andersen, and Rohit A Chavan, and Marina F Ponzio, and Rahul S Sawant, and Susana Rubiales de Barioglio, and Helgi B Schiöth, and Marta Fiol de Cuneo
Cátedra de Fisiología Humana, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, X5000ESU, Córdoba, Argentina. vcarlini@live.com.ar

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.

UI MeSH Term Description Entries
D008297 Male Males
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003511 Cyclohexanols Monohydroxy derivatives of cyclohexanes that contain the general formula R-C6H11O. They have a camphorlike odor and are used in making soaps, insecticides, germicides, dry cleaning, and plasticizers. Cyclohexanol
D005473 Fluoxetine The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. Fluoxetin,Fluoxetine Hydrochloride,Lilly-110140,N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine,Prozac,Sarafem,Lilly 110140,Lilly110140
D000069470 Venlafaxine Hydrochloride A cyclohexanol and phenylethylamine derivative that functions as a SEROTONIN AND NORADRENALINE REUPTAKE INHIBITOR (SNRI) and is used as an ANTIDEPRESSIVE AGENT. 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol HCl,Cyclohexanol, 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)-, hydrochloride,Dobupal,Efexor,Effexor,Sila-Venlafaxine,Trevilor,Vandral,Venlafaxine,Wy 45030,Wy-45,030,Wy-45030,Hydrochloride, Venlafaxine,Sila Venlafaxine,Wy 45,030,Wy45,030,Wy45030
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D017367 Selective Serotonin Reuptake Inhibitors Compounds that specifically inhibit the reuptake of serotonin in the brain. 5-HT Uptake Inhibitor,5-HT Uptake Inhibitors,5-Hydroxytryptamine Uptake Inhibitor,5-Hydroxytryptamine Uptake Inhibitors,SSRIs,Selective Serotonin Reuptake Inhibitor,Serotonin Reuptake Inhibitor,Serotonin Reuptake Inhibitors,Serotonin Uptake Inhibitor,Serotonin Uptake Inhibitors,Inhibitors, 5-HT Uptake,Inhibitors, 5-Hydroxytryptamine Uptake,Inhibitors, Serotonin Reuptake,Inhibitors, Serotonin Uptake,Reuptake Inhibitors, Serotonin,Uptake Inhibitors, 5-HT,Uptake Inhibitors, 5-Hydroxytryptamine,Uptake Inhibitors, Serotonin,Inhibitor, 5-HT Uptake,Inhibitor, 5-Hydroxytryptamine Uptake,Inhibitor, Serotonin Reuptake,Inhibitor, Serotonin Uptake,Reuptake Inhibitor, Serotonin,Uptake Inhibitor, 5-HT,Uptake Inhibitor, 5-Hydroxytryptamine,Uptake Inhibitor, Serotonin
D050486 Serotonin Plasma Membrane Transport Proteins Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SELECTIVE SEROTONIN REUPTAKE INHIBITORS. Neurotransmitter Transport Proteins, Serotonin-Specific,Neurotransmitter Transporters, Serotonin-Specific,Serotonin Plasma Membrane Transporter Proteins,5-Hydroxytryptamine Plasma Membrane Transport Protein,5HT Transporter,Platelet Serotonin Transporter,SERT Proteins,SLC6A4 Protein,Serotonectin,Serotonin Transporter,Serotonin Transporter, Platelets,Sodium-Dependent Serotonin Transporter,Solute Carrier Family 6, Member 4 Protein,5 Hydroxytryptamine Plasma Membrane Transport Protein,Neurotransmitter Transport Proteins, Serotonin Specific,Neurotransmitter Transporters, Serotonin Specific,Platelets Serotonin Transporter,Serotonin Transporter, Platelet,Serotonin Transporter, Sodium-Dependent,Serotonin-Specific Neurotransmitter Transporters,Sodium Dependent Serotonin Transporter,Transporter, Sodium-Dependent Serotonin
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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