Psychopharmacology

, 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

Abstract

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 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.

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.

Keywords

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

Notes

Acknowledgement

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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