The potent psychomotor, rewarding and reinforcing properties of 3‐fluoromethamphetamine in rodents

3‐fluoromethamphetamine (3‐FMA), a derivative of methamphetamine (METH), produces behavioral impairment and deficits in dopaminergic transmission in the striatum of mice. The abuse potential of 3‐FMA has not been fully characterized. The aim of this study was to evaluate the effects of 3‐FMA on locomotor activity as well as its rewarding and reinforcing properties in the conditioned place preference (CPP) and self‐administration procedures. Intravenous (i.v.) administration of 3‐FMA (0.5 and 1.0 mg/kg) significantly increased locomotor activity in a dose‐dependent manner in rats. In the CPP procedure, intraperitoneal administration of 3‐FMA (10 and 30 mg/kg) produced a significant alteration in place preference in mice. In the self‐administration paradigms, 3‐FMA showed drug‐taking behavior at the dose of 0.1 mg/kg/infusion (i.v.) during 2 hr sessions under fixed ratio schedules and high breakpoints at the dose of 0.3 and 1.0 mg/kg/infusion (i.v.) during 6 hr sessions under progressive ratio schedule of reinforcement in rats. A priming injection of 3‐FMA (0.4 mg/kg, i.v.), METH (0.2 mg/kg, i.v.), or cocaine (2.0 mg/kg, i.v.) reinstated 3‐FMA‐seeking behavior after an extinction period in 3‐FMA‐trained rats during 2 hr session. Taken together, these findings demonstrate robust psychomotor, rewarding and reinforcing properties of 3‐FMA, which may underlie its potential for compulsive use in humans. The study carried out to show whether 3‐fluoromethamphetamine (3‐FMA) has the psychopharmacological effects for the first time in the present study. The results showed that 3‐FMA increased 1) locomotor activity, 2) drug‐paired place preference, 3) reinstated 3‐FMA‐seeking behavior by re‐exposure of 3‐FMA, methamphetamine, or cocaine in multiple behavioral paradigms. Our findings demonstrate robust psychomotor, rewarding and reinforcing properties of 3‐FMA, which may underlie its potential for compulsive use in humans.