INHIBITION OF MORPHINE TOLERANCE WITHIN THE RAT NUCLEUS ACCUMBENS BY NITRIC OXIDE

The role of glutamate receptors within the nucleus accumbens in morphine tolerance has been postulated. Previous studies have reported that glutamate receptors exert their effects in part through the release of nitric oxide (NO). In the present study, the effect of intra-accumbal injections of L-arginine, the NO precursor and L-NAME, the NOS inhibitor on the morphine tolerance in Wistar rats (250-300 g) were investigated. For this purpose, male rats (n = 8/group) were anesthetized and bilateral cannulation (23-gauge, AP=1.7mm, L=±0.8, V= 7.1 mm) was performed into nucleus accumbens. Five days after cannulation, animals were trained in an Un-Biased conditioned place preference apparatus for five consecutive days. The NOergic drugs were injected in two ways: first; the animals were trained with morphine and were received L-arginine or L-NAME at 5th day of experiments just before the test. Second group received L-arginine or L-NAME before morphine injection. At the 5th day of the experiments, each animal was placed in the apparatus and its behavior was recorded for 10 min. The results showed that pretreatment of the animals with L-arginine did not produce any effect on morphine tolerance. Pretreatment of the animals with L-NAME potentiated both development and expression of morphine tolerance. In conclusion, present experiments showed that morphine tolerance is in part dependent on activation of NO system within the nucleus accumbens and the role of this neuromodulator in morphine dependence must be considered in further treatments of morphine addicts.