Changes Of Nitric Oxide And Neuronal Nitric Oxide Synthase In Morphine Dependent And Abstinent Rats

Objective:We explored the changes of serum nitric oxide level and neuronal nitric oxide synthase in morphine dependent and abstinent rats,in order to open out the relations of morphine addiction and nitric oxide.And try to provide a new target for studying clinic drugs by the changes of neuronal nitric oxide synthase.Methods: ⑴Rats were divided into four groups(10 for each group).Three were administered with morphine by intraperitoneal injection,tid.for 12 days.The doses of morphine infusion were added according toan escalating dose schedual so that the rats were dependented to morphine.Another group was injected with normal saline at the same way.Serum of morphine dependent group,morphine abstinence group were collected after 1h of the last injection.Serum of the spontaneousness abstinence 3d group was also collected.Serum of control group was collected after 1h of the last injection. NO was examined by using fluorescence spectrophotometer method. ⑵After male Sprayue-Dawley rats were divided into three groups, exprement group was administered with morphine by intraperitoneal injection,tid.for 12 days.The doses of morphine infusion were addedaccording toan escalating dose schedual so that the rats were dependented to morphine.Control group was injected with normal saline at the same way.Abstinent group was injected with a SC dose of 5mg/kg naloxone.One hour after the last injection , brains were removed and nNOS expression was studied by using immunohistochemical methods.Result: ⑴The values of serum NO of morphine dependent group and morphine abstinence group were(66.82±21.12)μmol/L and (86.82±18.68) μmol/L,which were higher than that of the control group(54.39±10.80) μmol/L repectively(p<0.05 p<0.01),and that of the spontaneousness abstinence 3d group was (59.99±14.19) μmol/L, had no difference compared with that of control group.(p>0.05). ⑵Morphine-dependence produce an increase in the number of nNOS-positive cells in the hippocampus,hypothalamus,cerebellum and locus coeruleus .The administration of naloxone to morphine-dependent rats to induce abstinence increased nNOS immuno-Reactivity in the hypothalamus and locus coeruleus.Conclusion: ⑴The level of serum NO raised in morphine dependent and abstinence,and that of the abstinence 3d had resumed. ⑵These results indicate that morphine-dependence and abstinence leads to alterations in nNOS expression in several important regions implicated in the physical tolerance and dependence to opiates and suggest the use of specific inhibitors of this isoform in this conditions.