title: Antidepressant action via the nitric oxide system: A pilot study in an acute depressive model induced by arginin.
abstract: Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P=0.011; hippocampus, P=0.011; midbrain, P=0.011; pons, P=0.013; striatum, P=0.011; and thalamus, P<0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P=0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD.
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. Electronic address: whisperoftheheart2@yahoo.co.jp.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshino
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ochi
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakata
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000208:Acute Disease; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001120:Arginine / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D005473:Fluoxetine / Q000627:therapeutic use; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000078764:Milnacipran; D000078785:Mirtazapine; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D001120:Arginine; D003521:Cyclopropanes; D005473:Fluoxetine; D008803:Mianserin; D000078764:Milnacipran; D000078785:Mirtazapine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant; Depression; Nitric oxide; Nitric oxide synthase; Rat