Multiple treatment potentiates the anticonvulsive activity of cholecystokinin octapeptides.
The dose-response curves for the anticonvulsive activity of sulfated and nonsulfated cholecystokinin octapeptide (CCK-8-SE and CCK-8-NS) against picrotoxin-induced (6 mg/kg SC) seizures were assessed either following or without pretreatment with a single high dose of CCK-8-SE or CCK-8-NS, to examine acute tolerance to the effect after IP injections in mice. As CCK-8-SE or CCK-8-NS pretreatment, a 1.6 mumole/kg dose was injected 2 hr prior to the second injection. No acute tolerance to the anticonvulsive activity was demonstrated, and CCK-8-NS pretreatment significantly potentiated its own anticonvulsive activity. Chronic (8-day) daily treatment with a 0.16 mumole/kg dose of CCK-8-SE or CCK-8-NS antagonized seizures by picrotoxin, presumably in a cumulative manner. To investigate the interactions of CCK octapeptides with other anticonvulsive agents, picrotoxin-induced seizures were antagonized with several doses of diazepam following or without acute, high-dose pretreatment with CCK-8-SE or CCK-8-NS. The two octapeptides only slightly modified the activity of diazepam: CCK-8-SE pretreatment displayed a tendency to antagonize it, while CCK-8-NS pretreatment to potentiate it. The results suggest that multiple treatment with CCK-8 induces sensitization of CCK receptors mediating anticonvulsive activity.
D000818:Animals; D000927:Anticonvulsants; D003975:Diazepam / Q000627:therapeutic use; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010852:Picrotoxin; D012640:Seizures / Q000188:drug therapy*; D012844:Sincalide / Q000008:administration & dosage / Q000627:therapeutic use*; D013464:Sulfuric Acids
D000927:Anticonvulsants; D003975:Diazepam; D010852:Picrotoxin; D012844:Sincalide; D013464:Sulfuric Acids