Involvement of nitric oxide within the rat central nucleus of amygdala in morphine tolerance

The role of glutamate receptor 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 effects of intra-accumbal injections of L-arginine (0.3, 1, and 3 ?g/rat), the NO precursor and L-NAME (0.3, 1, and 3 ?g/rat), the NOS inhibitor on the morphine tolerance were investigated in Wistar rats (250-300 g). Male rats (n = 8/group) were anesthetized and bilateral cannulation in nucleus accumbens (23-gauge, AP = 1.7 mm, 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 conscutive 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 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 have not showed any effects 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 to the activation of NO system within the nucleus accumbens and the role of this neuromodulator in morphine tolerance must be considered in further treatments of morphine addicts.