Effects of carbamazepine and baclofen on 4-aminopyridine-induced epileptic activity in rat hippocampal slices.
1. Rat transverse hippocampal slices exposed to 100 microM 4-aminopyridine (4-AP) generate spontaneous epileptic discharges ranging in duration from short 50 ms 'interictal' bursts to long 0.5-2 s 'polyspike' activity. 2. Here we compared the effects of the commonly used anticonvulsant, carbamazepine (40 microM) and the antispastic drug, baclofen (2 microM) on the various types of burst. 3. Carbamazepine completely abolished long bursts whilst leaving shorter bursts intact. This is consistent with its known anticonvulsant properties. 4. Baclofen greatly reduced the frequency of short bursts but did not block the long bursts. Rather, they became significantly more prolonged, indicating that baclofen does not have an anticonvulsant action, and may be proconvulsant. 5. These results conflict with conclusions based on studies using models that exhibited only interictal bursts, and emphasize the need to use experimental epilepsies which generate several types of epileptic discharge to evaluate the effects of putative anticonvulsant drugs. 6. The present findings suggest that GABAB receptors play a role in the transition of benign interictal bursts to longer polyspike activity which could develop into seizures in the whole animal.
Watts
A E
AE
Department of Physiology and Biophysics, St. Mary's Hospital Medical School, Imperial College, University of London.
Jefferys
J G
JG
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D002220:Carbamazepine; D015761:4-Aminopyridine; D001418:Baclofen