title: Protective effect of LY379268, a selective group II metabotropic glutamate receptor agonist, on dizocilpine-induced neuropathological changes in rat retrosplenial cortex.
abstract: In the present study, we examined the effects of LY379268, the group II metabotropic glutamate receptor (mGluR) agonist, on the neuropathological changes in the rat retrosplenial cortex induced by noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine ((+)-MK-801). Administration of LY379268 (1, 3, 10 mg/kg, i.p.) reduced dizocilpine (0.5 mg/kg, i.p.)-induced neuropathological changes in the retrosplenial cortex, in a dose-dependent manner. Co-administration of LY379268 (10 mg/kg, i.p.) with group II mGluR antagonist LY341495 (5 mg/kg, i.p.) blocked the effects of LY379268. Furthermore, LY379268 (10 mg/kg, i.p.) significantly reduced the expression of heat shock protein HSP-70, a marker of reversible neuronal injury, in the rat retrosplenial cortex after administration of dizocilpine (0.5 mg/kg, i.p.). Moreover, pretreatment with LY379268 (10 mg/kg, i.p.) significantly suppressed the increase in extracellular acetylcholine (ACh) levels in the retrosplenial cortex induced by administration of dizocilpine (0.5 mg/kg, i.p.). These results suggest that LY379268 has a protective effect on the neurotoxicity in the rat retrosplenial cortex after administration of NMDA receptor antagonists such as dizocilpine.
authors: Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan.
authors: Naoe
authors: N
authors: Okamura
authors: Kenji
authors: K
authors: Hashimoto
authors: Eiji
authors: E
authors: Shimizu
authors: Kaori
authors: K
authors: Koike
authors: Shintaro
authors: S
authors: Ohgake
authors: Hiroki
authors: H
authors: Koizumi
authors: Chikara
authors: C
authors: Kumakiri
authors: Naoya
authors: N
authors: Komatsu
authors: Masaomi
authors: M
authors: Iyo
mesh_terms: D000109:Acetylcholine / Q000032:analysis; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry / Q000187:drug effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000187:drug effects; D007150:Immunohistochemistry; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018691:Excitatory Amino Acid Antagonists; D018840:HSP70 Heat-Shock Proteins; C114624:LY 341495; C118218:LY 379268; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; D016291:Dizocilpine Maleate; D000109:Acetylcholine