Effects of sinomenine on NO/nNOS system in cerebellum and spinal cord of morphine-dependent and withdrawal mice / 生理学报

ABSTRACT

To explore the effect of sinomenine on the nitric oxide (NO)/neural nitric oxide synthase (nNOS) system in the cerebellum and spinal cord of morphine-dependent and morphine-withdrawal Kunming mice, mice were subjected to injection of morphine with an increasing dose for 5 d, and then were treated with sinomenine (40 mg/kg, i.p.) for another 5 d. Naloxone was used to develop acute withdrawal, and the withdrawal syndromes, including teeth chattering, twisting, straightening, sneezing and ptosis, were investigated. nNOS mRNA expressions in the cerebellum and spinal cord were determined by semi-quantitative RT-PCR. nNOS activity and NO level were determined by the chemistry-colorimetry and nitrate reductase-reduction, respectively. The results obtained were as follows (1) Sinomenine restored the decrease in body weight and alleviated the signs of morphine-withdrawal in mice. (2) Sinomenine also reduced the increases in nNOS mRNA expression and nNOS activity resulting from morphine-dependence, and simultaneously attenuated the high level of NO in both tissues following morphine-withdrawal. (3) Administration of sinomenine alone did not develop physical dependence in mice. The results obtained indicate that sinomenine may attenuate morphine addiction and significantly alleviate morphine-withdrawal symptoms, and the mechanism may be associated with the effect of sinomenine on the NO/nNOS system in the cerebellum and spinal cord.