D-Serine alleviates retrograde amnesia of a visual discrimination task in rats with a lesion of the perirhinal cortex

D-Serine has been suggested to be a potent endogenous glycine-site agonist on the N-methyl-D-aspartate receptor, thereby having a potential role in the process of learning and memory. In rats, perirhinal cortex (PC) constitutes a particularly important structure for mnemonic processing, and damage to this area induces both anterograde and retrograde amnesia. In the present work, we show that intraperitoneal administration of 1000 mg/kg D-serine immediately after bilateral lesion of PC produced complete restoration of retrograde memory in rats, measured by a visual brightness discrimination task, while a higher dose (3000 mg/kg) did not show any reliable effect. Uptake of the drug into the brain was confirmed using high performance liquid chromatography (HPLC). (C) 2003 Elsevier B.V. All rights reserved.