Glycine(B) receptor antagonists and partial agonists prevent memory deficits in inhibitory avoidance learning.

Abstract

Activation of N-methyl-d-aspartate (NMDA) receptors has been hypothesized to mediate certain forms of learning and memory. This hypothesis is based on the ability of competitive and uncompetitive NMDA receptor antagonists to disrupt learning. We investigated the effects of glycine site antagonists and partial agonists on deficits of acquisition (learning) and consolidation (memory) in a single trial inhibitory avoidance learning paradigm. Posttraining administration of either hypoxia (exposure to 7% oxygen) or the convulsant drug pentylenetetrazole (PTZ) (45 mg/kg) to mice impaired consolidation without producing neuronal cell death. Pretreatment with the competitive glycine antagonist 7-chlorokynurenic acid (7KYN) and the glycine partial agonists 1-aminocyclopropanecarboxylic acid (ACPC) and (+)HA-966 prevented memory deficits induced by hypoxia and PTZ, but did not affect scopolamine-induced learning impairment. In addition, ACPC prevented consolidation deficits evoked by a nonexcitotoxic concentration of l-trans-pyrrolidine-2, 4-dicarboxylate, a competitive inhibitor of glutamate transport that increases extracellular levels of glutamate. Moreover, (+)HA-966, 7KYN, and ACPC facilitated both acquisition and consolidation of inhibitory avoidance training, an effect that was dose-dependent and reversed by glycine. These results indicate that memory deficits induced by both hypoxia and PTZ involve NMDA receptor activation. Furthermore, the present findings demonstrate that glycine site antagonists and partial agonists prevent memory deficits of inhibitory avoidance learning by affecting consolidation, but not acquisition processes.

• Authors: E Viu, A Zapata, J Capdevila, P Skolnick, R Trullas
• Journal: Neurobiology of learning and memory (Neurobiol Learn Mem) Vol. 74 Issue 2 Pg. 146-60 (Sep 2000) ISSN: 1074-7427 [Print] United States
• PMID: 10933900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Excitatory Amino Acid Antagonists
• Muscarinic Antagonists
• Pyrrolidinones
• Receptors, Glycine
• Receptors, N-Methyl-D-Aspartate
• Glutamic Acid
• Dizocilpine Maleate
• Scopolamine
• 1-hydroxy-3-amino-2-pyrrolidone
• Kynurenic Acid
• 7-chlorokynurenic acid

Topics

• Animals
• Avoidance Learning (drug effects)
• Disease Models, Animal
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Glutamic Acid (metabolism)
• Inhibition, Psychological
• Kynurenic Acid (analogs & derivatives, pharmacology)
• Male
• Memory Disorders (prevention & control)
• Mice
• Muscarinic Antagonists (pharmacology)
• Pyrrolidinones (pharmacology)
• Receptors, Glycine (antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Retention, Psychology (drug effects)
• Scopolamine (pharmacology)