title: Effect of milnacipran on extracellular monoamine concentrations in the medial prefrontal cortex of rats pre-treated with lithium.
abstract: Antidepressants are effective in most patients with depression, but sometimes have sub-optimal effects. Thus, there is a need to use more powerful antidepressants when dealing with treatment-resistant cases. Lithium carbonate is widely used for this purpose. We investigated the acute effects of milnacipran, a serotonin-noradrenaline reuptake inhibitor, on extracellular serotonin, dopamine and noradrenaline concentrations, in the rat medial prefrontal cortex. The effects of milnacipran were examined in rats following 7 days of treatment with lithium, and in untreated controls. The lithium group had significantly greater basal levels of extracellular serotonin than the control group. Milnacipran (3 mg/kg) combined with lithium treatment caused a greater increase in extracellular noradrenaline and dopamine levels than milnacipran alone. Milnacipran (3 and 30 mg/kg) combined with lithium treatment also caused a greater increase in extracellular serotonin levels than milnacipran alone. Thus, lithium might augment the antidepressant effects of serotonin-noradrenaline reuptake inhibitors by augmenting serotonin release.
authors.affiliation: Department of Psychiatry, Neural Function, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan. ykita@med.hokudai.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitaichi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izumi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism*; D003521:Cyclopropanes / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D018020:Lithium Compounds / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D000078764:Milnacipran; D009638:Norepinephrine / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D003521:Cyclopropanes; D018020:Lithium Compounds; D012701:Serotonin; D000078764:Milnacipran; D004298:Dopamine; D009638:Norepinephrine