Pharmacological effects of metabotropic glutamate receptor ligands on prepulse inhibition in DBA/2J mice

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• 作者：Hirohiko Hikichi ; Miho Nishino ; Miyuki Fukushima ; Akio Satow ; Shunsuke Maehara ; Hiroshi Kawamoto ; Hisashi Ohta
• 关键词：mGlu receptor ; Prepulse inhibition ; DBA/2J (mouse)
• 刊名：European Journal of Pharmacology
• 出版年：2010
• 出版时间：10 August 2010
• 年：2010
• 卷：639
• 期：1-3
• 页码：99-105
• 全文大小：624 K

文摘

Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animals using acoustic prepulse inhibition of the startle. Both classical and atypical antipsychotics have been shown to improve prepulse inhibition in DBA/2J mice, a non-pharmacological model for impaired sensorimotor gating. The purpose of the present study was to clarify whether metabotropic glutamate receptors participate in control of sensorimotor gating. We evaluated various metabotropic glutamate receptor ligands on prepulse inhibition in DBA/2J mice. This basal level of prepulse inhibition in DBA/2J mice was increased by only the mGlu₁ receptor antagonists [2-cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one] (CFMTI), 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-α]benzimidazole-2-carboxamide hydrochloride (YM-298198), and (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)-methanone (JNJ16259685). There was no effect after treatments with the mGlu₅ receptor antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), the mGlu_2/3 receptor agonist (−)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), the mGlu_2/3 receptor antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), the mGlu₇ receptor agonist N,N′-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the mGlu₇ receptor antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazonolo[4,5-c]pyridin-4(5H)-one (MMPIP), or the mGlu₈ receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG). These findings indicate that inhibition of mGlu₁ receptor selectively increases prepulse inhibition in DBA/2J mice and suggest that mGlu₁ receptor antagonists could be a novel treatment for some aspects of schizophrenia.