The role of inducible-nitric oxide in cocaine-induced kindling

Experimentally naive male Sprague Dawley rats (weighing 85-110 g) were used to examine the role of inducible nitric oxide synthase (iNOS) in cocaine-i nduced kindling. Repeated administration of cocaine 145 mg/kg, ip) to Sprag ue Dawley male rats for 7 consecutive days produced a progressive increase in the convulsive responsiveness and death. Pretreatment with iNOS inhibito rs, L-N-6-(1-iminoethyl)lysine (NIL; 10 mg/kg, ip) and (-)epigalloocatechin gallate (EGCG; 10 mg/kg, ip) 30 min before cocaine (45 mg/kg, ip) administ ration for 7 days attenuated the development of cocaine kindling and blocke d cocaine-induced death. Results of NMDA receptor binding assay in the hipp ocampus showed a significant increase in the affinity without changes in th e density in animals treated with cocaine, but there were no changes in the se parameters in the cortex. Pretreatment with NIL or EGCG prior to cocaine administration abolished the cocaine-induced effect in the NMDA receptor a ffinity in the hippocampus, These results suggest that iNOS induction follo wed by an increase of NMDA receptor affinity in the hippocampus after repea ted exposure to cocaine may participate in the process of the development o f cocaine kindling.