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


OBJECTIVE
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.
Specialization Area of Experimental Psychology, Hacettepe University, Ankara, Turkey.
Umut
U
Ulusu
I Tayfun
IT
Uzbay
Hakan
H
Kayir
Tevfik
T
Alici
Sirel
S
Karakas
D000818:Animals; D021461:Animals, Outbred Strains; D001120:Arginine / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D009538:Nicotine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D009569:Nitric Oxide / Q000502:physiology*; D013997:Time Factors
D009569:Nitric Oxide; D009538:Nicotine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester