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-induced kindling. Repeated administration of cocaine (45 mg/kg, i.p.) to Sprague Dawley male rats for 7 consecutive days produced a progressive increase in the convulsive responsiveness and death. Pretreatment with iNOS inhibitors, L-N6-(1-iminoethyl)lysine (NIL; 10 mg/kg, i.p.) and (-)-epigalloocatechin gallate (EGCG; 10 mg/kg, i.p.) 30 min before cocaine (45 mg/kg, i.p.) administration for 7 days attenuated the development of cocaine kindling and blocked cocaine-induced death. Results of NMDA receptor binding assay in the hippocampus showed a significant increase in the affinity without changes in the density in animals treated with cocaine, but there were no changes in these parameters in the cortex. Pretreatment with NIL or EGCG prior to cocaine administration abolished the cocaine-induced effect in the NMDA receptor affinity in the hippocampus. These results suggest that iNOS induction followed by an increase of NMDA receptor affinity in the hippocampus after repeated exposure to cocaine may participate in the process of the development of cocaine kindling.
Park
K K
KK
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee 32307, USA.
Reuben
J S
JS
Soliman
K F
KF
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000378:metabolism*; D003292:Convulsants / Q000008:administration & dosage / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism
D003292:Convulsants; C090663:N(6)-(1-iminoethyl)lysine; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003042:Cocaine; D008239:Lysine