Nitric oxide modulates state dependency induced by lithium in an inhibitory avoidance task in mice

Behav Pharmacol. 2007 Jul;18(4):289-95. doi: 10.1097/FBP.0b013e3281f520b0.


The effect of intracerebroventricular (i.c.v.) injections of L-arginine, a nitric oxide (NO) precursor and L-NAME, an inhibitor of NO synthase, on retrieval of state-dependent memory induced by LiCl (lithium) was investigated. A one-trial step-down inhibitory avoidance task was used for memory assessment in adult male NMRI mice. Intraperitoneal administration of lithium (10 mg/kg), immediately after training, impaired memory on the test day. Pretest administration of different doses of lithium (5, 10 and 20 mg/kg) reversed the impairment of memory caused by posttraining lithium (10 mg/kg). In addition, pretest administration of L-arginine (0.001, 0.01 and 0.1 microg/mouse, i.c.v.) or L-NAME (0.001, 0.01 and 0.1 microg/mouse, i.c.v.) also reversed amnesia induced by posttraining lithium. Furthermore, pretest coadministration with lithium of a dose of L-arginine (0.0001 microg/mouse, i.c.v.) or L-NAME (0.0001 microg/mouse, i.c.v.) that had no effects when administered alone, increased the effect of lithium on retrieval of inhibitory avoidance memory. The results suggest that NO may have a modulatory role on state-dependent retrieval of inhibitory avoidance memory induced by lithium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimanic Agents / pharmacology*
  • Arginine / pharmacology
  • Avoidance Learning / drug effects*
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Injections, Intraventricular
  • Lithium Chloride / pharmacology*
  • Male
  • Memory / drug effects*
  • Mice
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide Synthase


  • Antimanic Agents
  • Enzyme Inhibitors
  • Arginine
  • Nitric Oxide Synthase
  • Lithium Chloride
  • NG-Nitroarginine Methyl Ester