Pre-training prevents context fear conditioning deficits produced by hippocampal NMDA receptor blockade

Neurobiol Learn Mem. 2003 Sep;80(2):123-9. doi: 10.1016/s1074-7427(03)00040-6.


These experiments explore parallels between the neurobiological substrates of spatial and context learning. Male Long-Evans rats were employed in a context fear conditioning protocol that involved sequential acquisition and testing in two distinct contexts. Rats received three unsignaled footshocks in one context and were tested for context fear, measured as freezing, the next day. Four days later, the procedure was repeated in a different, distinct context. Rats received a hippocampal infusion of either the NMDA receptor antagonist 5-amino-phosphonovaleric acid (APV, 10 microg) or vehicle prior to training in each context. NMDA receptor blockade was effective in impairing context learning only in the first context. Context fear acquisition was not impaired by APV in the second context, indicating that pre-training (in the first context) mitigated the effects of APV. These data agree with those seen previously in the water maze, where pre-training prevented learning deficits produced by NMDA receptor blockade. The data thus suggest that the neurobiological substrates of context learning and place learning overlap.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Conditioning, Classical / drug effects*
  • Fear*
  • Female
  • Hippocampus / drug effects*
  • Learning / drug effects
  • Male
  • Rats
  • Rats, Long-Evans
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Valine / analogs & derivatives*
  • Valine / pharmacology*


  • Receptors, N-Methyl-D-Aspartate
  • 2-amino-5-phosphopentanoic acid
  • Valine