Protective effect of LY379268, a selective group II metabotropic glutamate receptor agonist, on dizocilpine-induced neuropathological changes in rat retrosplenial cortex.
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.
Okamura
Naoe
N
Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan.
Hashimoto
Kenji
K
Shimizu
Eiji
E
Koike
Kaori
K
Ohgake
Shintaro
S
Koizumi
Hiroki
H
Kumakiri
Chikara
C
Komatsu
Naoya
N
Iyo
Masaomi
M
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
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