Evidence for the role of nitric oxide in nicotine-induced locomotor sensitization in mice

Psychopharmacology (Berl). 2005 Apr;178(4):500-4. doi: 10.1007/s00213-004-2018-0. Epub 2004 Oct 9.


Rationale: Nitric oxide (NO) is implicated in both acute effects of addictive drugs and development of dependence to them. We investigated the role of NO in nicotine-induced locomotor sensitization.

Objectives: The effects of Nomega-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, and a combination of a NO precursor L-arginine and L-NAME on nicotine-induced locomotor sensitization were investigated in Swiss Webster mice.

Methods: Sensitization to psychomotor stimulating effect of nicotine was rendered by seven injections of nicotine (1 mg/kg) on every other day. To investigate their effect on the development of sensitization to nicotine, L-NAME (15-60 mg/kg) and L-arginine (1 g/kg) were given before nicotine administration during the first seven sessions. To investigate the effect of these compounds on the expression of nicotine sensitization, after a 4-day drug-free period another group of mice received a challenge injection of nicotine on day 18.

Results: Nicotine (1 mg/kg) produced a robust locomotor sensitization in mice. The doses of 30 mg/kg and 60 mg/kg of L-NAME blocked the development of sensitization to nicotine; and, L-arginine (1 g/kg) pretreatment reversed this effect of L-NAME. Likewise, the doses of 30 mg/kg and 60 mg/kg of L-NAME inhibited the expression of sensitization to nicotine on day 18; and, L-arginine (1 g/kg) pretreatment reversed this inhibitory effect of L-NAME.

Conclusions: Our results suggest that NO is implicated in the development and expression of nicotine-induced locomotor sensitization in mice.

Publication types

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

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Arginine / administration & dosage
  • Arginine / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Mice
  • Motor Activity / drug effects*
  • Motor Activity / physiology*
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / antagonists & inhibitors
  • NG-Nitroarginine Methyl Ester / pharmacokinetics
  • Nicotine / administration & dosage
  • Nicotine / antagonists & inhibitors
  • Nicotine / pharmacokinetics*
  • Nitric Oxide / physiology*
  • Time Factors


  • Nitric Oxide
  • Nicotine
  • Arginine
  • NG-Nitroarginine Methyl Ester