Effect of selective bilateral destruction of the substantia nigra on antiepileptic drug actions in kindled rats.
The substantia nigra (SN) is thought to be involved in the regulation of seizure activity and there is evidence that the nigra might be a site of anticonvulsant drug action, especially in the case of drugs that act by potentiating gamma-aminobutyric acid (GABA)-mediated neurotransmission. The current studies monitored the anticonvulsant effect of four major antiepileptic drugs, i.e. valproic acid, carbamazepine, phenobarbital and diazepam, in fully kindled rats before and after bilateral destruction of the SN. Rats were kindled by stimulation of either the basolateral amygdala or the piriform cortex. The SN was lesioned bilaterally by microinjection of ibotenic acid, and only animals with near-complete, selective destruction of the SN were used for final evaluation of the anticonvulsant drug experiments. The behavioural characteristics and the duration of fully kindled seizures were not altered by bilateral destruction of the SN. Phenobarbital, diazepam and valproate significantly reduced kindled seizures severity and duration before and after the SN lesions. Carbamazepine was the only drug to show a marked decrease in its anticonvulsant effects after SN lesion. Since benzodiazepines, valproate and phenobarbital are though to enhance GABAergic transmission, the lack of effect of SN lesions on the anticonvulsant effects of these drugs argues against the suggestion that the SN is the anatomical site responsible for exerting anticonvulsant effects in response to drug-induced augmentation of GABA transmission.
Wahnschaffe
U
U
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, F.R.G.
Löscher
W
W
D000679:Amygdala / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology; D004566:Electrodes; D005260:Female; D007051:Ibotenic Acid / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000502:physiology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000033:anatomy & histology / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D007051:Ibotenic Acid; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D003975:Diazepam; D010634:Phenobarbital