Acquisition, extinction, and reinstatement of Pavlovian fear conditioning: the roles of the NMDA receptor and nitric oxide

Brain Res. 2000 Feb 28;857(1-2):66-70. doi: 10.1016/s0006-8993(99)02388-4.


The acquisition and extinction of Pavlovian conditioned fear have been shown to be mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor. This study found that the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801) blocked the reinstatement of Pavlovian conditioned fear in rats. The role of nitric oxide (NO) in the acquisition and extinction of Pavlovian fear conditioning was also examined. L-NAME, an NO synthase inhibitor, failed to block the acquisition or extinction of Pavlovian fear conditioning. The results are discussed in the context of hierarchical associations and the array of NMDA and calcium mediated mechanisms of synaptic strengthening.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Avoidance Learning / physiology*
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology*
  • Dizocilpine Maleate / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology*
  • Fear / drug effects*
  • Fear / physiology*
  • Fear / psychology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / metabolism*


  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Nitric Oxide
  • Dizocilpine Maleate
  • NG-Nitroarginine Methyl Ester