The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice

Abstract The tendency of a psychostimulant to increase locomotion in rodents is considered be associated with its addictive properties. Mephedrone, one the most popular psychoactive substances used recreationally, known enhance locomotor activity mice, but little about potential development tolerance central effects. In present study, we decided evaluate possible involvement L-arginine-NO-cGMP pathway mephedrone-induced hyperlocomotion. Experiments were performed on adult male Albino Swiss and was measured automatically. Our work indicated that 5-day administration L-NAME (25 or 50 mg/kg/day), methylene blue (5 10 L-arginine hydrochloride (i.e., 250 mg/kg/day) prevented hyperlocomotion, whereas treatment at dose 125 mg/kg/day potentiated this effect mephedrone. Summarizing, our data revealed contributes mephedrone’s effects since inhibition signalling via blocking NOS NO-stimulated sGC As for cGMP-regulated phosphodiesterases, probably they are not involved these mechanisms.