Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester.

The hypothesis that an arginine-nitric oxide (NO) synthase-NO system mediates the morphine abstinence syndrome was tested in adult male rats implanted subcutaneously for 3 days with one morphine (75 mg) pellet followed by naloxone-precipitated withdrawal (0.5 mg/kg). Injection with a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (NAME, 100 mg/kg subcutaneous), shortly before naloxone-induced withdrawal significantly inhibited abstinence signs by 25-80%. Continuous infusion of NAME via subcutaneous osmotic pumps during the development of morphine physical dependence and during naloxone-precipitated withdrawal also inhibited morphine abstinence signs. In addition, treatment with isosorbide dinitrate, a NO donor, induced a quasi morphine-abstinence syndrome (QMAS) that was significantly suppressed by implantation of a morphine pellet 3 days before isosorbide dinitrate treatment. These results indicate that NO mediates part of the expression of the morphine abstinence syndrome.

Antagonism of alcohol-induced suppression of rat testosterone secretion by an inhibitor of nitric oxide synthase.

To examine whether nitric oxide (NO) mediates the suppression of testosterone secretion by alcohol (ethanol), adult male rats were pretreated with a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (NAME), then treated with alcohol. Serum and testicular interstitial fluid (TIF) testosterone concentrations, serum luteinizing hormone (LH) concentrations, blood alcohol concentrations (BAC), and TIF volumes were measured 2 hr after alcohol treatment at a time of peak effects of alcohol and NAME on testosterone secretion. Pretreatment with NAME (30 or 100 mg/kg, subcutaneous) 30 min before alcohol treatment (0.5-3 g/kg, intraperitoneal) completely blocked the alcohol-induced suppression of testosterone secretion into the general circulation and into TIF without significantly altering blood alcohol concentrations (BAC) or TIF volumes. These results support the hypotheses that NO synthase inhibitors can antagonize alcohol-induced suppression of testicular steroidogenesis, that alcohol interacts with arginine-NO synthase systems that regulate testicular steroidogenesis, and that NO is involved in mediating alcohol's testicular and reproductive effects.