PMID: 8959046Oct 31, 1996Paper

One-way cross-sensitization and cross-tolerance to seizure activity from cocaine to lidocaine

Annals of the New York Academy of Sciences
K ShimosatoT Saito

Abstract

The present study examined the effects of daily treatment with a subconvulsant dose (50 mg/kg) of cocaine or lidocaine on susceptibility to seizures induced by cross-injections of the same dose of the other local anesthetic, and to seizures induced by pentylenetetrazol (PTZ) or N-methyl-DL-aspartate (NMDLA) in ddY mice. Repeated administration of 50 mg/kg cocaine caused the development of sensitization to cocaine-induced seizures during an initial 3 or 4 days, followed by the development of tolerance on days 4-6. The same dose of lidocaine, however, produced little or no seizure activity following repeated administration. In contrast, when injected 24 hr after 2-4 days of cocaine treatment, 50 mg/kg lidocaine produced severe seizures. Interestingly, this cross-sensitization from cocaine to lidocaine diminished upon further cocaine treatment. In contrast, treatment with lidocaine for 2-6 days had no effect on subsequent changes in seizure susceptibility following repeated cocaine injections. Neither treatment with cocaine nor lidocaine for 2 or 5 days influenced susceptibility to seizures induced by a challenge injection of PTZ (50 mg/kg, i.p.) or NMDLA (300 mg/kg, i.p.) 24 hr after treatment. HPLC analyses revealed that the coc...Continue Reading

References

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