title: Distinct effects of the serotonin-noradrenaline reuptake inhibitors milnacipran and venlafaxine on rat pineal monoamines.
abstract: Monoamine systems are involved in the pathology and therapeutic mechanism of depression. The pineal gland contains large amounts of serotonin as a precursor for melatonin, and its activity is controlled by noradrenergic sympathetic nerves. Pineal diurnal activity and its release of melatonin are relevant to aberrant states observed in depression. We investigated the effects on pineal monoamines of serotonin-noradrenaline reuptake inhibitors, which are widely used antidepressants. Four days of milnacipran treatment led to an increase in noradrenaline and serotonin levels, whereas 4 days of venlafaxine treatment reduced 5-hydroxyindoleacetic acid levels; both agents induced an increase in dopamine levels. Our data suggest that milnacipran increases levels of the precursor for melatonin synthesis by facilitating the noradrenergic regulation of pineal activity and that venlafaxine inhibits serotonin reuptake into noradrenergic terminals on the pineal gland.
authors.affiliation: aDepartment of Anatomy I, Showa University School of Medicine, Tokyo bLaboratory of Pathology, Food and Drug Safety Center, Division of Toxicology, Hatano Research Institute, Kanagawa cDepartment of Physiology, Saitama Medical University, Saitama, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Muneoka
authors.forename: Makiko
authors.initials: M
authors.lastname: Kuwagata
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Shioda
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000032:analysis*; D003521:Cyclopropanes / Q000494:pharmacology*; D008297:Male; D000078764:Milnacipran; D009638:Norepinephrine / Q000032:analysis; D010870:Pineal Gland / Q000737:chemistry* / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D003521:Cyclopropanes; D000078764:Milnacipran; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride