EFFECTS OF ANTICONVULSIVE DRUGS ON PENTYLENETETRAZOL KINDLING AND LONG-TERM POTENTIATION IN FREELY MOVING RATS

Drugs with anticonvulsive properties and different mechanisms of actio n were compared for their influence on long-term potentiation and pent ylenetetrazol kindling in freely moving animals. Rats were chronically implanted with a stimulation electrode in the angular bundle and a re cording electrode in the dentate gyrus. Field potentials in the dentat e gyrus were elicited and long-term potentiation was induced by stimul ation of the perforant pathway. The clinically used drugs or the poten tially anticonvulsive drugs, diphenylhydantoin (50 mg/kg), diazepam (0 .5 mg/kg), pentobarbital (10 mg/kg), dizocilpine (MK 801, 0.2 mg/kg) a nd CGP 43487 (2-amino-4-methyl-5-phosphono-3-pentenoic acid-carboxyeth ylester, 10 mg/kg), were injected before tetanization. In behavioural experiments pentylenetetrazol kindling was performed with pretreatment with the substances in dosages indicated above (except MK 801, 0.3 mg /kg). Field potentials recorded in the interval between drug administr ation and tetanization were influenced only by diphenylhydantoin which enhanced the population spike amplitude to 128% of control values. Ho wever, the substances showed different effects on long-term potentiati on. MK 801, CGP 43487 and pentobarbital depressed potentiation; diazep am was without effect. Diphenylhydantoin had a minor influence on indu ction but significantly impaired maintenance of long-term potentiation Furthermore, MK 801, CGP 43487, diazepam and pentobarbital differenti ally depressed kindling whereas phenytoin only slightly influenced it. The consequences as to hypothetical common cellular mechanisms for ki ndling development and long-term potentiation are discussed. (C) 1998 Elsevier Science B.V. All rights reserved.