نقش نيتريك اكسايد موجود در هسته آكومبانس بر القاء تحمل انگيزشي به مرفين در موش صحرايي نر

The prevalence of opioid addiction is relatively high in Iran. Since the mechanism of opioid addiction has not been well understood, this social problem is still remained unresolved. In the present study, the effect of nitric oxide within the nucleus accumbens on the acquisition and expression of morphine tolerance was investigated using an unbiased conditioned place preference (CPP) paradigm in male Wistar rats (200-250 g). For this purpose, morphine (2.5, 5, and 7.5 mg/kg) was administered to induce CPP. Seven days after surgery and cannulation, animals received morphine (12.5, 25, and 50 mg/kg, for three consecutive days) in order to develop tolerance to morphine. Administration of low and high doses of nitric oxide precursor L-arginine (0.3 and 3 µg/rat) into the nucleus accumbens on the testing day increased and decreased the expression of morphine incentive tolerance respectively. In addition, intra-accumbens injection of low and moderate doses of nitric oxide synthase inhibitor L-NAME (0.3 and 1 µg/rat) enhanced the expression of morphine incentive tolerance and an injection of a high dose of this drug (3 µg/rat) attenuated the latter response. Meanwhile, low-dose administration of L-arginine (0.3 µg/rat) before morphine (12.5, 25, and 50 mg/kg) had no effect on the development of morphine tolerance. On the other hand, higher doses of L-arginine (1 and 3 µg/rat) decreased the development of morphine tolerance. Furthermore, injection of L-NAME (0.3, 1, and 3 µg/rat) into the nucleus accumbens enhanced the development of morphine tolerance. It can be concluded that nitric oxide within nucleus accumbens may have an important role in the expression and development of morphine tolerance.