Enhancement of contextual fear-conditioning by putative (±)-α-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators and N-methyl-D-aspartate (NMDA) receptor antagonists in DBA/2J mice

Ying Lu, Jeanne M. Wehner

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies demonstrated that DBA/2J (DBA) mice performed poorly while C57BL/6J (C57) mice performed normally on a number of complex learning and memory tasks. Chronic oxiracetam treatment dramatically improved the performance of DBA mice but not that of C57 mice on the Morris water task and in contextual fear conditioning. The present study demonstrates that acute treatment with nootropics, oxiracetam (10-1000 mg/kg) or aniracetam (10-100 mg/kg), and N-methyl-D-Aspartate (NMDA) antagonists, (+)-MK-801 (0.1-3 μg/kg), CPP (0.01-0.3 mg/kg), and (+)-HA-966 (0.1-3 mg/kg), administered prior to training and testing, reversed the contextual learning impairment in DBA mice in a dose-dependent manner without affecting auditory cue conditioning. These effects appeared to be independent of testing order (context vs. auditory cue tests) and were not due to state-dependent learning. The inactive stereoisomers, (-)-MK-801 and (-)-HA-966, were incapable of increasing contextual freezing in DBA mice. In DBA mice, the effects of 30 mg/kg oxiracetam and 100 mg/kg aniracetam were inhibited by the (±)-α-amino-3-hydroxy-5-methylisoxazole-4-pro pionic acid (AMPA) receptor antagonists, NBQX, and GYKI-52466. The combined administration of 30 mg/kg oxiracetam and 1 μg/kg (+)-MK-801 produced an additive response. None of the pharmacological treatments altered performance in C57 mice at doses that were effective in DBA mice. These results suggest that DBA mice may be learning impaired due to altered glutamatergic receptor function.

Original languageEnglish (US)
Pages (from-to)197-207
Number of pages11
JournalBrain Research
Volume768
Issue number1-2
DOIs
StatePublished - Sep 12 1997

Keywords

  • AMPA antagonist
  • Aniracetam
  • C57 mouse
  • Contextual fear conditioning
  • DBA mouse
  • NMDA antagonist
  • Oxiracetam

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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