Fluvoxamine, a selective serotonin reuptake inhibitor, suppresses tetrahydrobiopterin in the mouse hippocampus. 2004

H Miura, and H Qiao, and T Kitagami, and T Ohta
Department of Psychiatry, School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. hmiura@med.nagoya-u.ac.jp

In the present study, we investigated the effects of fluvoxamine, a selective serotonin reuptake inhibitor, on brain tetrahydrobiopterin (BH4) levels. We directly measured levels of BH4 by Tani and Ohno's direct method as well as the serotonin (5-HT) turnover ratio, i.e. 5-hydroxyindoleacetic acid (5-HIAA)/5-HT, after sub-acute s.c. injection of fluvoxamine in the hippocampus of mice. Our animal model incorporated two risk factors of depression, social isolation and acute environmental change. Male ddY mice (6W) were housed in isolation (1 per cage; 35 days), injected with fluvoxamine (20 or 40 mg/kg; days 29-35), and exposed to novelty stress (20 min; day 35). In the stress session, behavioral parameters, i.e. total distance and rearing behavior, were measured. Isolation housing increased both behaviors. Fluvoxamine attenuated rearing behavior, but did not influence total distance. Isolation housing increased BH4 levels. Novelty stress increased BH4 levels in group housing, although it did not change them in isolation housing. Fluvoxamine suppressed BH4 levels. In isolation housing, fluvoxamine increased 5-HT turnover ratios, while it decreased them in group housing. In conclusion, fluvoxamine, housing condition, and novelty stress regulated BH4 levels. Fluvoxamine may have changed behavior and 5-HT turnover by suppressing BH4 levels as well as by inhibiting 5-HT reuptake.

UI MeSH Term Description Entries
D008297 Male Males
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
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
D001708 Biopterins Pterin derivatives based on 2-amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone. Biopterins are natural products that have been considered as growth factors for some insects. Biopterins are cofactors for the AROMATIC AMINO ACID hydroxylases and NITRIC OXIDE SYNTHASE. Deficiencies in BIOPTERINS metabolism (e.g., lowered TETRAHYDROBIOPTERIN) are associated with neurological deterioration (e.g., HYPERPHENYLALANINAEMIA). 2-Amino-6-((1S,2R)-1,2-dihydroxypropyl)-4(1H)-pteridinone,2-Amino-6-((1S,2S)-1,2-dihydroxypropyl)-4(1H)-pteridinone,2-Amino-6-(1,2-dihydroxypropyl)-4(8H)-pteridinone,2-amino-6-((1R,2R)-1,2-dihydroxypropyl)-4(3H)-pteridinone,4(1H)-Pteridinone, 2-amino-6-(1,2-dihydroxypropyl)-, (S-(R*,S*))-,6-Biopterin,Biopterin,D-threo-Biopterin,L-Biopterin,L-erythro-Biopterin,L-threo-Biopterin,2-Amino-6-(1,2-dihydroxypropyl)-4(1H)-pteridinone,Dictyopterin,Orinapterin,6 Biopterin,D threo Biopterin,L Biopterin,L erythro Biopterin,L threo Biopterin
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D012934 Social Isolation The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. Isolation, Social,Social Exclusion,Exclusion, Social,Social Exclusions
D013312 Stress, Physiological The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions. Biotic Stress,Metabolic Stress,Physiological Stress,Abiotic Stress,Abiotic Stress Reaction,Abiotic Stress Response,Biological Stress,Metabolic Stress Response,Physiological Stress Reaction,Physiological Stress Reactivity,Physiological Stress Response,Abiotic Stress Reactions,Abiotic Stress Responses,Abiotic Stresses,Biological Stresses,Biotic Stresses,Metabolic Stress Responses,Metabolic Stresses,Physiological Stress Reactions,Physiological Stress Responses,Physiological Stresses,Reaction, Abiotic Stress,Reactions, Abiotic Stress,Response, Abiotic Stress,Response, Metabolic Stress,Stress Reaction, Physiological,Stress Response, Metabolic,Stress Response, Physiological,Stress, Abiotic,Stress, Biological,Stress, Biotic,Stress, Metabolic
D016666 Fluvoxamine A selective serotonin reuptake inhibitor that is used in the treatment of DEPRESSION and a variety of ANXIETY DISORDERS. DU-23000,Desiflu,Dumirox,Faverin,Fevarin,Floxyfral,Fluvoxadura,Fluvoxamin AL,Fluvoxamin Stada,Fluvoxamin beta,Fluvoxamin-neuraxpharm,Fluvoxamin-ratiopharm,Fluvoxamina Geminis,Fluvoxamine Maleate,Fluvoxamine Maleate, (E)-Isomer,Fluvoxamine, (Z)-Isomer,Luvox,Novo-Fluvoxamine,Nu-Fluvoxamine,PMS-Fluvoxamine,ratio-Fluvoxamine,DU 23000,DU23000,Fluvoxamin neuraxpharm,Fluvoxamin ratiopharm,Geminis, Fluvoxamina,Novo Fluvoxamine,Nu Fluvoxamine,PMS Fluvoxamine,ratio Fluvoxamine
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

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