On the requirement of nitric oxide signaling in the amygdala for consolidation of inhibitory avoidance memory

Neurobiol Learn Mem. 2009 Mar;91(3):266-72. doi: 10.1016/j.nlm.2008.09.016. Epub 2008 Oct 31.


Evidence suggests that the NO/sGC/PKG pathway plays a key role in memory processing but the actual participation of this signaling cascade in the amygdala during memory consolidation remains unknown. Here, we show that when infused in the amygdala immediately after inhibitory avoidance training, but not later, the NO synthase inhibitor L-NNA hindered long-term memory retention without affecting locomotion, exploratory behavior, anxiety state or retrieval of the avoidance response. The amnesic effect of L-NNA was not state-dependent and was mimicked by the soluble guanylyl cyclase inhibitor LY83583 and the PKG inhibitor KT-5823. On the contrary, post-training intra-amygdala infusion of the NOS substrate L-Arg, the NO-releasing compound SNAP or the non-hydrolysable analog of cGMP 8Br-cGMP increased memory retention in a dose-dependent manner. Co-infusion of 8Br-cGMP reversed the amnesic effect of L-NNA and LY83583 but not that of KT-5823. Our data indicate that the NO-induced activation of PKG in the amygdala is a necessary step for consolidation of inhibitory avoidance memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / administration & dosage
  • Amygdala / physiology*
  • Animals
  • Anxiety
  • Arginine / metabolism
  • Avoidance Learning / physiology*
  • Carbazoles / administration & dosage
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism
  • Enzyme Inhibitors / administration & dosage
  • Exploratory Behavior / drug effects
  • Guanylate Cyclase / antagonists & inhibitors
  • Male
  • Maze Learning / physiology
  • Memory / drug effects
  • Memory / physiology*
  • Motor Activity / drug effects
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Penicillamine / analogs & derivatives
  • Penicillamine / metabolism
  • Rats
  • Rats, Wistar
  • Signal Transduction*


  • Aminoquinolines
  • Carbazoles
  • Enzyme Inhibitors
  • S-nitro-N-acetylpenicillamine
  • KT 5823
  • Nitric Oxide
  • 6-anilino-5,8-quinolinedione
  • Arginine
  • Nitric Oxide Synthase
  • Guanylate Cyclase
  • Penicillamine
  • Cyclic GMP