Cocaine increases inducible nitric oxide synthase expression in rats: effects of acute and binge administration

The present studies assessed the effects of acute and binge cocaine administration on the in vivo production of inducible nitric oxide synthase in a rat model of endotoxemia. Inducible nitric oxide synthase is a key enzyme involved in host defense and inflammatory responses consequent to infection through its production of nitric oxide. Male Lewis rats received subcutaneous injections of saline or selected doses of cocaine (7.5-30 mg/kg) at the same time as a 50 microg/kg dose of lipopolysaccharide (LPS). Animals in the binge cocaine experiments received two additional injections of cocaine or saline at 2 and 4 h after the initial injections. All animals were sacrificed 6 h after initial drug administration and tissues harvested for determination of iNOS protein levels. Plasma nitrite/nitrate levels were also assayed to assess any treatment-related differences in the degradative by-products of nitric oxide metabolism. Western blot analyses of iNOS expression indicated that both acute and binge cocaine treatment resulted in significant increases in iNOS expression in all tissues assayed. Furthermore, acute and binge cocaine treatment also dose-dependently increased plasma nitrite levels. These data suggest that cocaine may impact resistance to gram-negative infections and severity of these infections via modulation of nitric oxide parameters.