, Volume 178, Issue 4, pp 500–504 | Cite as

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

  • Umut Ulusu
  • I. Tayfun Uzbay
  • Hakan Kayir
  • Tevfik Alici
  • Sirel Karakas
Original Investigation



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.


The effects of Nω-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.


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.


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.


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


Locomotor sensitization l-NAME l-Arginine Nicotine Nitric oxide Mice 



This study was supported by the State Planning Institution and Ministry of Defense of the Turkish Government (Grant No: MSB-3, 99K120150).


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Umut Ulusu
    • 1
  • I. Tayfun Uzbay
    • 2
  • Hakan Kayir
    • 2
  • Tevfik Alici
    • 2
  • Sirel Karakas
    • 1
  1. 1.Specialization Area of Experimental PsychologyHacettepe UniversityAnkaraTurkey
  2. 2.Department of Medical Pharmacology, Psychopharmacology Research UnitGulhane Military Medical AcademyAnkaraTurkey

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