Subsensitivity to muscimol-induced catalepsy after long-term administration of phenytoin in rats.
Male albino rats were injected with 25 mg/kg of phenytoin (PHT) every day for 20 consecutive days and were tested on days 21 and 28 for their response to 1 or 2 mg/kg of muscimol, a GABA receptor agonist. Rats treated with PHT showed a decreased responsiveness to muscimol-induced catalepsy (2 mg/kg) on day 21 but not on day 28. Acutely administered PHT, on the contrary, had a tendency to potentiate muscimol-induced catalepsy. Muscimol-induced catalepsy was not antagonized by acute treatment with bicuculline (0.5-2.0 mg/kg). It is proposed that withdrawal after long-term administration of PHT reduces the sensitivity of a GABA receptor site not sensitive to bicuculline.
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D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D002375:Catalepsy / Q000139:chemically induced*; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009118:Muscimol / Q000008:administration & dosage*; D010080:Oxazoles / Q000008:administration & dosage*; D010672:Phenytoin / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D010080:Oxazoles; D011963:Receptors, GABA-A; D009118:Muscimol; D010672:Phenytoin; D001640:Bicuculline