NITRIC OXIDE MEDIATION OF MORPHINE SENSITIZATION IN THE RAT NUCLEUS ACCUMBENS

Previous studies have reported that morphine exerts its effects in part through the release of nitric oxide (NO). It has been pustulated that drug sensitization is a major cause of relapse to drug use in addicts. In the present study the effects of intra-accumbal injections of L-arginine, the NO precursor and L-NAME, the NOS inhibitor on the morphine sensitization in Wistar rats (250-300 g) were investigated. Male rats (n = 8/group) were anesthetized and bilateral cannulation in nucleus accumbens (23-gauge, AP = 1.7mm, L = ±0.8, V = 7.1 mm) was performed. Five days after cannulation, animals were trained in an Un-Biased conditioned place preference apparatus for five consecutive days. The NOergic drugs were injected to the animals 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 augments the development, but reduced the expression of morphine sensitization. Pretreatment of the animals with L-NAME reduced both development and expression of morphine sensitization. In conclusion, present experiments showed that morphine sensitization is in part dependent on the 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.