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

• Published in: Psychopharmacologia 2005-04, Vol.178 (4), p.500-504
• Main Authors: ULUSU, Umut, UZBAY, I. Tayfun, KAYIR, Hakan, ALICI, Tevfik, KARAKAS, Sirel
• Format: Article
• Language: English
• Subjects: Animals; Animals, Outbred Strains; Arginine - administration & dosage; Arginine - pharmacokinetics; Biological and medical sciences; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Medical sciences; 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; Tobacco, tobacco smoking; Toxicology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-004-2018-0

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 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. 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.