Potentiation of morphine-induced conditioned place preference with concurrent use of amantadine and fluvoxamine by the intraperitoneal and intracerebroventricular injection in rat

In this study, the effect of concurrent use of fluvoxamine and amantadine on morphine-induced conditioned place preference (CPP) was investigated by the intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection in rat. The CPP paradigms took place on 6 consecutive days by using an unbiased procedure. Our results showed that i.p. injection of morphine sulfate (2.5–10 mg/kg) induced CPP in rat. On day 6, fluvoxamine (5 and 10 mg/kg, i.p.), and amantadine (5 and 10 mg/kg, i.p.) both increased morphine-induced conditioned place preference. Intracerebroventricular injection of fluvoxamine (10 μg/rat) and amantadine (10 μg/rat) were also increased morphine-induced conditioned preference significantly. Concurrent use of fluvoxamine (5 mg/kg, i.p.; 10 μg/rat i.c.v.) and amantadine (10 mg/kg, i.p.; 10 μg/rat, i.c.v.) potentiated morphine-induced conditioned preference significantly. Release of dopamine from neurons cause reinforcing behavior. Morphine produces reinforcement (reward) effect by activation of μ receptors which facilitated dopaminergic transmission through dopamine release. Fluvoxamine, a serotonin reuptake inhibitor, increase serotonin concentration in synaptic clefts, which is a potent stimulator of dopamine release. Amantadine also appears to work by increasing dopamine release from neuron. In conclusion, our results show that concurrent use of fluvoxamine and amantadine potentiate morphine-like effect on CPP through increasing dopaminergic transmission and this combination may simulate the rewarding effect of morphine and can be candidate for controlling the drug compulsive seeking in morphine dependent subjects.