Prophylaxis of amygdala kindling-induced epileptogenesis: comparison of a GABA uptake inhibitor and diazepam.
The prophylactic effect of an inhibitor of synaptosomal GABA uptake, SK&F 89976-A (N-[4,4-diphenyl-3-butenyl]-nipecotic acid), on the development of amygdala kindled seizures was studied in adult female rats. For comparative purposes, the action of diazepam was also investigated. Dosages of SK&F 89976-A and diazepam which were previously shown to be the ED50 for seizure inhibition in fully kindled rats (15 mg/kg and 2 mg/kg i.p., respectively) were administered daily 30 min prior to amygdala stimulation in naive, unkindled rats. Both drugs inhibited the evolution of full kindled seizure activity and markedly suppressed kindling-associated increases in the duration of behavioral and electrographic seizures. Control rats developed fully kindled stage 5 seizures after 8.9 +/- 1.1 amygdala stimulations but drug-treated rats did not progress beyond an early stage of kindled seizures as long as the animals were treated with the drugs (22 days). Diazepam produced significant CNS depressant effects throughout the course of administration but SK&F 89976-A prevented kindling with no depressant side effects. The ability of SK&F 89976-A and diazepam to inhibit the development of full amygdala kindled seizures may be related to enhancement of central inhibitory GABAergic systems.
Schwark
W S
WS
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853-6401.
Haluska
M
M
D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D007696:Kindling, Neurologic / Q000187:drug effects*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D003975:Diazepam