en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: For centuries, cannabinoids are known to be effective in pain relief. Itch is an unpleasant sensation that provokes a desire to scratch. Since itch and pain are two sensations sharing a lot in common, we aimed to investigate whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behavior and also observe whether modulation of nitric oxide (NO) production mediates the antipruritic effect of WIN 55,212-2.<br> <strong>Methods</strong>: Scratching behavior is induced by intradermal injection of serotonin (50 &micro;g/50 &micro;L/mouse) to BALB/c mice. The cannabinoid agonist WIN 55,212-2 (1, 3, 10 mg/kg, IP) was given 30 min before serotonin injection. To observe the effect of NO modulation on the antipruritic effect of cannabinoids, the endothelial nitric oxide synthase (NOS) inhibitor L-NAME (3 mg/kg, IP), the neuronal NOS inhibitor 7-nitroindazole (3 mg/kg, IP), and the NO precursor L-arginine (100 mg/kg, IP) were administered together with WIN 55,212-2.&nbsp;<br> <strong>Results</strong>: WIN 55,212-2 reduced serotonin-induced scratches at higher doses (3, 10 mg/kg; P<0.0001). The endothelial NOS inhibitor L-NAME, the neuronal NOS inhibitor 7-nitroindazole, and the nitric oxide precursor L-arginine did not influence the antipruritic action of WIN 55,212-2. When NO modulators were used alone, only the neuronal NOS inhibitor 7-nitroindazole attenuated serotonin-induced scratches (P<0.0001).<br> <strong>Conclusion</strong>: Our findings indicate that exogenous cannabinoids may attenuate serotonin-induced scratches and NO does not mediate the antipruritic effect of WIN 55,212-2. On the other hand, neuronal NOS inhibition may play a role in the production of serotonin-induced scratches.</div> Cannabinoid system, Nitric oxide, Pruritus, Serotonin, WIN 55,212-2 473 480 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1348-1&slc_lang=en&sid=1 Oyku Zeynep Gercek oykuzeynepgercek@gmail.com 13700319475328460028776 13700319475328460028776 No Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Turkey. Busra Oflaz busraoflaz@hotmail.com 13700319475328460028777 13700319475328460028777 No Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Turkey. Neslihan Oguz neslihan_ogz@hotmail.com 13700319475328460028778 13700319475328460028778 No Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Turkey. Koray Demirci koraydemirci6@hotmail.com 13700319475328460028779 13700319475328460028779 No Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Turkey. Ozgur Gunduz gunduz_ozgur@yahoo.com 13700319475328460028780 13700319475328460028780 No Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Turkey. Ahmet Ulugol aulugol@trakya.edu.tr 13700319475328460028781 13700319475328460028781 Yes Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Turkey.