title: Effect of co-administration of a serotonin-noradrenaline reuptake inhibitor and a dopamine agonist on extracellular monoamine concentrations in rats.
abstract: Recent studies have shown that dopamine agonists are useful for the treatment of not only Parkinson's disease, but also major depressive disorders. However, while these dopamine agonists provide a new treatment strategy for major depressive disorders, such as treatment-resistant cases, the antidepressant effect of dopamine agonists has yet to be investigated. To examine the mechanism of the antidepressive effect of dopamine agonists, we investigated the acute effect of the dopamine receptor agonist, cabergoline, and the serotonin-noradrenaline reuptake inhibitor, milnacipran, on extracellular noradrenaline, dopamine and serotonin concentrations in the rat medial prefrontal cortex. There was a greater increase in extracellular noradrenaline concentrations when acute milnacipran (30 mg/kg intraperitoneally) was administered after acute high-dose cabergoline (1 and 2 mg/kg subcutaneously) than when acute milnacipran was administered following acute vehicle or low-dose cabergoline (0.25 mg/kg subcutaneously). There were no significant differences noted in the dopamine or serotonin concentrations. These results suggest that the addition of cabergoline has the potential to strengthen the antidepressant effects of milnacipran and that the mechanism of action of the antidepressive effect of dopamine agonists might be due to enhancement of induced increases of extracellular noradrenaline.
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: Takeshi
authors.initials: T
authors.lastname: Izumi
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Teruaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Masui
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D000077465:Cabergoline; D003521:Cyclopropanes / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; 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; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D000077465:Cabergoline; D003521:Cyclopropanes; D004298:Dopamine; D018491:Dopamine Agonists; D004873:Ergolines; D000078764:Milnacipran; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors