title: Metabotropic glutamate 2/3 receptor antagonists improve behavioral and prefrontal dopaminergic alterations in the chronic corticosterone-induced depression model in mice.
abstract: Metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists have an antidepressant-like effect, but the exact mechanism still remains unclear. This study examined the effects of mGlu2/3 receptor antagonists in chronic corticosterone-treated mice which could be used as an animal model of depression. In the forced swim test, the mGlu2/3 receptor antagonists MGS0039 (1.0 mg/kg, i.p.) and LY341495 (0.3 mg/kg, i.p) significantly reduced the increased immobility time of mice pretreated with corticosterone (20 mg/kg, s.c.) for 21 days, while desipramine (30 mg/kg, i.p.) and fluoxetine (30 mg/kg, i.p.) did not. The antidepressant-like effect of LY341495 was not blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor antagonist NBQX (10 mg/kg, i.p.). Systemic administration of LY341495 did not affect basal release of glutamate, dopamine or serotonin in the prefrontal cortex of the control or chronic corticosterone-treated mice. Chronic corticosterone markedly enhanced high K(+)-induced release of dopamine, but not serotonin or glutamate, in the prefrontal cortex. This neurochemical change was blocked by systemic administration of MGS0039 and LY341495, but not desipramine or fluoxetine. These results suggest that chronic corticosterone-treated mice could be used as an animal model of treatment-resistant depression. This study also suggests that the prefrontal dopaminergic system is involved in the antidepressant-like effect of mGlu2/3 receptor antagonists in the chronic corticosterone-induced depression model.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Koji
authors.initials: K
authors.lastname: Yano
authors.forename: Ryota
authors.initials: R
authors.lastname: Araki
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kita
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Onoe
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Chaki
authors.forename: Atsuro
authors.initials: A
authors.lastname: Nakazato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Akemichi
authors.initials: A
authors.lastname: Baba
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003345:Corticosterone / Q000633:toxicity*; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D004298:Dopamine; D003345:Corticosterone