Involvement of dynorphin A in the inhibition of morphine physical dependence by N-nitro-L-arginine in rats

摘要

Objective To investigate the involvement of immunoreactive-dynorphin A in the inhibitory effect of N-nitro-L-arginine on the morphine physical dependence in rats. Methods The rats were rendered dependent on morphine by subcutaneous administration of morphine solution three times daily in a manner of dose increment of 5 mg·kg~(-1) for 6 days. The degree of morphine physical dependence was monitored by scoring the abstinence syndromes precipitated by 5 mg·kg~(-1) naloxone of the rats. The expression levels of immunoreactive dynorphin A in tissues were determined using a radioimmunoassay. Results Intraperitoneal injection of 5 mg·kg~(-1) N-nitro-L-arginine suppresses most of the withdrawal symptoms of morphine dependent rats. N-nitro-L-arginine can elevate the expression of immunoreactive dynorphin. Conclusions Chronic N-nitro-L-arginine administration can inhibit the development of morphine physical dependence in a manner of dose-dependence, which is significantly related to its role of regulating the endogeneous dynorphin system.