Sulpiride injections into the medial septum reverse the influence of intra-medial septum injection of L-arginine on expression of place conditioning-induced by morphine in rats.

Effects of intra-medial septum injections of L-arginine, a precursor of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, and sulpiride, a selective antagonist of dopamine D2 receptor on morphine-induced conditioned place preference (CPP) in male Wistar rats were examined. Using a 3-day schedule of conditioning, morphine (0.5-7.5 mg/kg, s.c.) produced a significant place preference in a dose-dependent manner. The maximum response was observed with 5.0 mg/kg of opioid. Sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-arginine (0.3, 1.0 and 3.0 microg/rat) or L-NAME (0.3, 1.0 and 3.0 microg/rat), in combination with morphine (5.0 mg/kg), during conditioning, significantly altered morphine-induced CPP. Single doses (0.3, 1.0 and 3.0 microg/rat) of either L-arginine or L-NAME, during conditioning, did not induce CPP. Sulpiride at 0.3-3.0 microg/rat, intra-medial septum, during conditioning, produced a significant conditioned place aversion. Intra-medial septum injections of L-arginine but not L-NAME or sulpiride, 1-2 min before testing, increased the expression of morphine-induced CPP. The administration of sulpiride (0.3, 1.0 and 3.0 microg/rat), but not L-NAME (0.3, 1.0 and 3.0 microg/rat), 1-2 min before the injection of L-arginine (0.3 microg/rat) on day of test, significantly attenuated the response to L-arginine. L-Arginine (0.3-3.0 microg/rat), during conditioning, showed a statistically significant increase in locomotor activity compared with that to control group. Moreover, sulpiride decreased locomotion by itself or in combination with morphine during conditioning and on the test day of morphine CPP. It can be concluded that L-arginine, a precursor of nitric oxide, in the rat median septum may play a role in expression of morphine conditioning due to dopamine release in this area.