The Effect of Concurrent Injection of Amantadine and Paroxetine on Positive Reinforcing Effect of Morphine in Conditioned Place Preference(CPP) Model in Mice

Increased level of dopamine in accumbens nucleus has a key role in the rewarding effects or positive reinforcement of abused drugs, whereas serotonin facilitates dopamine release in brain. The aim of this study was to investigate the effect of concurrent use of amantadine and paroxetine on reinforcing effect of morphine in conditioned place preference model in mice. In this experimental study male NMRI mice (20-30 g) were used within 6 consecutive days including preconditioning, conditioning and postconditioning phases. On the first day, after removal of the partitions, time spent in every 3 compartments was measured for 10 minutes. After determination of low and high preferred side, animals received morphine sulfate (5 mg/kg) intraperitoneally on the 2nd and 4th days in the least preferred side, but on the 3rd and 5th days of the test, animals received saline (10ml/kg) in high preferred side. On the test day or postconditioning phase, animals received amantadine, and paroxetine alone or their concurrent does, instead of morphine. Control group received saline in both sides (n = 8). Our results show that morphine significantly and dose dependently (2.5, 5,10 mg/kg) induced CPP (P<0.001). Amantadine, only in doses of 5 and 10 mg /kg (P<0.01, P<0.001, respectively) induced CPP. Paroxetine induced CPP in all doses. Concurrent use of amantadine(10mg/kg) and paroxetine (10mg/kg) significantly enhances morphine - like CPP (P <0.001). Concurrent use of drugs, releases dopamine and inhibit reuptake of serotonin, and may potentiate morphine-like CPP and could be useful in decreasing some opioid withdrawal signs.