Journal of Rafsanjan University of Medical Sciences

  Effects of Nitric Oxide on The Expression of Nicotine and Apomorphine Induced Behavioral Sensitization in Mice

  A. Shirazi [1] , N. Osanloo [2] , M. AllafJavadi [3] , H. Sahraei [4] , M. Khosravi²

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  Background and Objective : Nicotine is the most abused drug in the world Experiments have shown that repeated administration of nicotine may increase the responsibility to the drug, whereas small amounts of nicotine may increase behavioral responses including locomotor activity. The aim of the present study was to investigate the role of nitric oxide and possible dopamine mediation in nicotine-induced behavioral sensitization. Since, it is hypothesized that dopaminergic pathways within the brain are responsible for sensitization, apomorphine has been used. Apomorphine was also used to evaluate the interactions between nitric oxide and brain dopaminergic pathways.

  Materials and Methods: In the present study, the effects of L-arginine (a nitirc oxide precursor) and L-NAME (a nitric oxide synthase inhibitor) on the acquisition and expression of nicotine-induced behavioral sensitization in female N-MARI mice (body weight 20-25 g n=7/group) were investigated. Animal activities were recorded by an infrared activity meter. In order to evaluate the effetcs of the drugs on animal locomotor activity, animals were received different doses of nicotine (0.25, 0.5, 0.75, 1 and 1.5 mg/kg), L-arginine (5, 10, 20 and 50 mg/kg), L-NAME (5, 10 and 20 mg/kg) apomorphine (0.125, 0.5 and 2 mg/kg). L-arginine and/or L-NAME were injected to the animals either 20 min before each nicotine or apomorphine administration during the sensitization phase (acquisition) or 20 min before nicotine or apomorphine challenge dose (expression).

  Results: Results showed that administration of nicotine (1 mg/kg) caused significantly reduced, while apomorphine (0.125 mg/kg) significantly increased in animal's locomotor activity. While L-arginine administration did not change the animals' activities, injection of L-NAME (10 and 20 mg/kg) significantly reduced animals activities. Administration of L-arginine (5-50 mg/kg) before nicotine injection did not affect the nicotine-induced behavioral sensitization but did inhibit apomorphine-induced behavioral senitization. Injection of L-arginine (5-50 mgkg) reduced the expression of behavioral sensitization in nicotine and apomorphine senstized mice. L-NAME (5, 10 and 20 mg/kg) injection reduced both acquisition and expression of nicotine and apomorphine-induced behavioral sensitization.

  Conclusion: It could be concluded that inhibition of nitric oxide synthesis caused the inhibition of behavioral sensitization to nicotine and apomorphine. Considering these findings, it seems that nitric oxide inhibits nicotine-induced behavioral sensitization via brain dopaminergic pathways.

  Key Words: Nicotine Nitric Oxide L-Arginine locomotion Sensitization Apomorphine.

  [1] BSc, Dept. of Physiology and Biophysics, School of Medicine, and Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran.

  [2] Assistant Professor, Dept. of Biology, School of Science, North Tehran Branch, Islamic Azad University, Tehran

  [3] Academic Member, School of Nursing, Baqiyatallah University of Medical Sciences, Tehran

  [4] Associate Professor, Dept. of Physiology and Biophysics, Baqiyatallah University of Medical Sciences, Tehran

  (Corresponding author) Tel: (021)22281561, Fax: (021)22281561, E-mail: h.sahraei@bmsu.ac.ir