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

Abstract

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 selfadministration 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-FMAseeking 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 Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents

“…The open-field test was performed as described previously [16]. Mice were acclimated to the open-field arena in an illuminated and sound-attenuated cubicle for at least 6 days (for 30 min/day).…”

“…The CPP experiment was performed based on our previous study [16]. The CPP apparatus (MED-CPP-3013-2, Med Associates) consisted of two large compartments (17.4 cm × 12.7 cm × 12.7 cm) separated by a guillotine door.…”

“…The mice that stayed over 960 s on either side during the pre-conditioning test were excluded from this study. The cutoff value (>960 s) for biased preference was determined by our previous study [16]. During the conditioning phase, the mice were given an i.p.…”

“…In the post-conditioning phase, each mouse was allowed to roam freely between the both sides of the apparatus for 20 min. A preference score was determined by calculating the difference between the times spent in the drug-paired side of the apparatus during the pre-versus post-conditioning phases, as described previously [16].…”

“…In addition, the rewarding and reinforcing properties of psychostimulants such as cocaine, methamphetamine, and PCP have been well demonstrated through various behavioral assessments including open-field test, conditioned place preference (CPP), and intravenous (i.v.) drug self-administration paradigms [14][15][16]. In previous studies, PCP and PCP derivatives produced robust increases in locomotor activity [17,18] and CPP in rodents [18][19][20].…”