The role of hippocampal nitric oxide (NO) on learning and immediate, short- and long-term memory retrieval in inhibitory avoidance task in male adult rats

Behav Brain Res. 2009 Jul 19;201(1):166-72. doi: 10.1016/j.bbr.2009.02.011. Epub 2009 Feb 21.


There is impressive amount of evidence suggesting the involvement of nitric oxide (NO) in hippocampal synaptic plasticity and consequently learning and memory. Hippocampus is a brain region which is widely implicated in several types of learning and memory formation, including inhibitory avoidance learning. Since the CA1 region of hippocampus has shown nitric oxide synthase (NOS) activity, inhibition of the NOS enzymes can modulate hippocampal function, hence affecting memory processes. Therefore, we conducted series of experiments to further investigate the role of NO on inhibitory avoidance short- and long-term memory in rats. For this purpose, male Wistar rats were divided into 15 groups (n=10), and bilaterally implanted with guide cannulae aimed at the CA1 region of hippocampus. Animals received pre-training, post-training and pre-retrieval injections of vehicle (saline) or different doses of L-NAME (5, 10 and 15 microg/0.5 microl/side) or l-arginine (alone or in combination with L-NAME), tested for immediate, short- and long-term memory retention in an inhibitory avoidance task. Our results indicated that step-through latency (STL) of short- and long-term memory retention test was significantly reduced in L-NAME treated rats (15 microg/0.5 microl for immediate and short-term memory; 10 microg/0.5 microl for long-term memory), as compared to that of control group. Results also revealed that, L-arginine produced no any significant effect on STL, however could reverse the effect of L-NAME on memory. Our results also showed that, blocking of NO signaling immediately after training had no effect on either short- or long-term memory, indicating that NO release only during training, and not during consolidation, plays a role in memory formation. Together, our findings suggest that NO synthase inhibition by L-NAME can induce impairments in immediate, short- and long-term memories of inhibitory avoidance task, and these impairments are dependent on the learning and memory processes at which NOS inhibited.

MeSH terms

  • Analysis of Variance
  • Animals
  • Arginine / administration & dosage
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Catheterization
  • Electroshock
  • Enzyme Inhibitors / administration & dosage
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology*
  • Microinjections
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Wistar
  • Retention, Psychology / drug effects
  • Retention, Psychology / physiology*


  • Enzyme Inhibitors
  • Nitric Oxide
  • Arginine
  • NG-Nitroarginine Methyl Ester