Endogenous Opioids Regulate the Expression of Inducible Nitric Oxide Synthase by Splenocytes1

In the present study, we tested the hypothesis that lipopoly-saccharide (LPS)-induced expression of nitric oxide synthase (iNOS) by splenocytes is modulated through the activation of endogenous opioids in the central nervous system. The initial studies determined the parameters of LPS-induced expression of iNOS by splenocytes. Rats were injected with LPS at doses of 0, 1, 10, 100, and 1000 mg/kg, and measures of both iNOS mRNA and protein showed a dose-dependent increase in ex-pression. In a time course study, rats received 100 mg/kg LPS and were killed at 0, 2, 4, 8, and 16 h postinjection. Both iNOS mRNA and protein expression was detectable at the 2-h time point, with peak expression occurring at 8 h. To evaluate the involvement of endogenous opioids, the opioid receptor antag-onist naltrexone was administered at 0, 0.1, 1, or 10 mg/kg s.c