Task-specific enhancement of short-term, but not long-term, memory by class I metabotropic glutamate receptor antagonist 1-aminoindan-1,5-dicarboxylic acid in rats

Pharmacological application of broad agonists and antagonists has supported the notion of a potential role of metabotropic glutamate receptors (mGluRs ) in learning and memory formation, but the specific function of the differ ent classes or individual subtypes remains elusive. Furthermore, our knowle dge with respect to different learning mechanisms is still fragmentary. In an attempt to clarify further the function of mGluRs in learning, rats were trained in various paradigms in the presence/absence of the specific class I antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA). Intraperitoneal ap plication of AIDA prior to training led to enhanced within-session performa nce in animals trained in a positively reinforced reference memory task in a three-choice maze. However, this enhancement did not result in increased retention as measured by the number of correct responses during the first f our trials of each session on subsequent days. The increase was purely an e nhancement in within-session performance, required doses higher than 2 mg/k g, and was not accompanied by an unspecific increase in activity as monitor ed in the open field. By contrast, AIDA animals trained in a combined shock -reinforced contextual and cue conditioning paradigm demonstrated a pronoun ced retention deficit compared with controls in conditioning to the context , but not the cue (a high-frequency tone). Although within-session performa nce during context and cue periods was slightly increased in the AIDA group , the difference did not reach significance. Drug-induced hyperactivity, wh ich could account for the memory deficit, was excluded by recordings of act ivity in specific activity cages. These results shed new light on the possi ble function of class I mGluRs in learning and memory formation and imply t hat systemic blockade of class I mGluRs may enhance short-term memory under certain learning conditions. (C) 1999 Elsevier Science B.V. All rights res erved.