Nitric Oxide Synthase Activity and the Level of Nitrates/Nitrites in Brain Regions during Spontaneous Morphine Withdrawal in Rats

Activity of nitric oxide synthase (NOS) and concentrations of nitrate/nitrites (NOx-) were measured in brain regions of rats during spontaneous morphine withdrawal, which was modeled in male Wistar rats. The animals were injected with the increasing intraperitoneal doses (10-100 mg/kg, twice a day) of morphine hydrochloride for 6 days. Thirty six hours after the last injection the severity of the spontaneous morphine withdrawal syndrome was determined by specific autonomic and locomotor indices The withdrawal was accompanied by the increase of both NOS activity and NOx- levels in the midbrain and hippocampus, the decrease of these parameters in striatum and hypothalamus, and lack of changes in cerebral cortex and brain stem. In cerebellum NOS activity decreased whereas NOx- concentrations remained unchanged. In the cerebral cortex, striatum, midbrain, and cerebellum activity of NOS and NOx- concentrations correlated with the withdrawal syndrome severity and also with the specific signs of abstinence.