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Seizures and Brain Injury in Neonatal Rats Induced by 1 S,3R-ACPD, a Metabotropic Glutamate Receptor Agonist



The role of metabotropic excitatory amino acid receptors in seizures and brain injury was examined using the selective metabotropic agonist 1 S,3R-ACPD [ ( 1 S,3R)-1-aminocyclopentane-1-3-dicarboxylic acid] in 7-d-old neonatal rats. Systemic administration of 1 S,3R-ACPD produced dose-dependent convulsions (ED,, = 16 mg/kg, i.p.) that were stereoselective for the active metabotropic ACPD isomer, since lR,BS-ACPD was less potent (ED,, = 93 mg/kg, i.p.). 1 S,3R-ACPD-induced seizures were antagonized by systemic administration of dantrolene, an inhibitor of intracellular calcium mobilization, but not by the ionotropic glutamate antagonists MK-601 or GYKI-52466. As indexed by hemispheric brain weight differences 5 d postinjection, unilateral intrastriatal injection of 1 S,3R-ACPD (0.1-2.0 ccrnoll PI), but not lR,SS-ACPD, produced dose-dependent brai

Year: 2013
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