A comparative study on the effect of L-arginine and morphine in induction of conditioned place preference in rat

It has been shown that L-arginine like the abused drugs could release dopamine from meso-cortico-limbic system. The purpose of the present study was to compare the effect of L-arginine with morphine as a standard abuse drug in the induction of conditioned place preference (CPP) in rat. For this purpose, male Wistar rats (250-300 g) were used in the experiments. Five days after surgical cannulation in the ventral tegmental area (VTA), different doses of L-arginine, L-NAME or morphine were injected and conditioned biased method was preformed. The results showed that: 1. Intraperitoneal (i.p.) (0.1, 1 and 5 mg/kg) but not intra-VTA (i-VTA) (0.3, 0.1 and 3 µg/rat) injections of L-arginine induced CPP in a dose-dependent manner. Injection of 10 mg/kg (i.p.) and 2 µg/rat of morphine (i-VTA) also caused a significant CPP in rats. Both i.p. (0.1, 1 and 5 mg/kg) and i-VTA (0.3, 0.1 and µg/rat) injection of L-NAME did not produce any effect in the rats, but the drug at higher dose (5 mg/kg, i.p.) attenuated the CPP induced by L-arginine (5 mg/kg, i.p.) Administration of morphine (10 mg/kg, i.p.) on three consecutive days and, then with 3-day interval caused the occurrence of sensitization to morphine, so that injection of ineffective dose of morphine (0.5 mg/kg, i.p.) induced CPP in sensitized rats. However, when the procedure was repeated for L-arginine (5 mg/kg, i.p.), rats showed negative response to the ineffective dose of L-arginine (0.1 mg/kg, i.p.). Meanwhile, in rats that received L-arginine (5 mg/kg, i.p.) on training days, injection of the same dose L-arginine on the test day dramatically decreased the time spent in drug-paired side while injection of morphine (10 mg/kg, i.p.) on the test day to those rats which had received morphine (10 mg/kg, i.p.) on training days caused an increase in time spent in the drug-paired compartment. It could be concluded that i.p. injection of L-arginine causes significant CPP rats and this behavior was attenuated by nitric oxide synthase inhibitor, L-NAME. Furthermore, the site of action of the drug seems not to be VTA. On the other hand behaviors due to administration of L-arginine did not show some properties of abused drugs such as sensitization and state dependency.