Role of cerebral spermidine in the development of sensitization to convulsant activity of cocaine and lidocaine.
We have previously shown that daily treatment with subconvulsant dose of cocaine resulted in the elevation of brain levels of polyamines such as putrescine and spermidine and the development of increased susceptibility to cocaine-induced seizures. The present study examined whether exogenously administered polyamines affect seizure activity caused by various doses of cocaine and lidocaine in mice. Thirty minutes after intracerebroventricular treatments with either saline, putrescine or spermidine (1-4 mumol), animals were injected intraperitoneally with cocaine or lidocaine (60-90 mg/kg); then the occurrence of clonic seizures was observed. Spermidine enhanced cocaine-induced seizure activity, while putrescine had no effect on it. Lidocaine-induced convulsions were also dose-dependently potentiated by spermidine. In addition, spermidine significantly enhanced seizure activity following an injection of N-methyl-DL-aspartate. The results suggest that spermidine plays an important role in the development of sensitization to convulsant activity by cocaine and lidocaine via modulation of N-methyl-D-aspartate receptors.
Shimosato
K
K
Department of Pharmacology, Kawasaki Medical School, Okayama, Japan.
Watanabe
S
S
Katsura
M
M
Ohkuma
S
S
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D003292:Convulsants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004361:Drug Tolerance; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007275:Injections, Intravenous; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D011700:Putrescine / Q000008:administration & dosage / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013095:Spermidine / Q000008:administration & dosage / Q000494:pharmacology*
D003292:Convulsants; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D008012:Lidocaine; D003042:Cocaine; D013095:Spermidine; D011700:Putrescine