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The RhoA gene showed an important genotypic association with nicotine dependence and smoking initiation. The current study aims to investigate the effect of the Rho GTPase inhibitor ML141 in the progression of nicotine dependence in a mice model of precipitated nicotine withdrawal syndrome by mecamylamine.The experimental procedure involved administration of 2.5 mg/kg nicotine dissolved in normal saline subcutaneously (s.c) four times a day consecutively for 7 days and last single dose in the morning on 8^th day. ML-141 was dissolved in dimethyl sulfoxide (DMSO) and was administered daily with nicotine as corrective treatment at a dose of 1,5 and 10 mg/kg (p < 0.05). An injection of 3 mg/kg of mecamylamine intraperitoneal (ip) was given an hour later than the last nicotine dose on the day 8 to precipitate withdrawal of nicotine and withdrawal severity was assessed by measuring hyperalgesia …