Effect of Combined Dopaminergic and GABA‐ergic Stimulation on Ouabain‐Induced Epileptiform Activity

Abstract

In this study we tested a hypothesis that dopamine and GABA receptor-stimulating agents given together might mutually potentiate their anticonvulsant activities. To test this hypothesis, experiments were performed on free-moving rabbits with epileptiform activity evoked by cortical application of ouabain. After combined treatment with apomorphine and GHBA 3 out of 6 animals displayed no EEG epileptiform activity, and in the remaining 3 rabbits this activity was greatly reduced. A combined pretreatment with apomorphine and GHBA abolished epileptiform EEG activity during the first hour and shortened it during the second hour, but not significantly. Apomorphine given together with amino-oxyacetic acid before ouabain completely abolished the epileptiform activity in 4 out of 6 animals. In the remaining 2 rabbits the latency of ouabain affect was prolonged, the epileptiform activity during the first hour was abolished, and it was markedly decreased during the next 2 hr (significantly from controls or groups receiving apomorphine or amino-oxyacetic acid). Phenytoin was less potent than apomorphine with GHBA or apomorphine given together with AOAA. The animals' behavior was observed.

Electrophysiological and Structural Aspects in the Frontal Cortex After the Bee (Apis mellifera) Venom Experimental Treatment

“…1b. Such abnormal electric discharges are known to be produced by phospholipase A2 (PLA2) isolated from BV (Clapp et al, 1995;Gandolfo et al, 1996), but they seem to constitute a common reaction of neurons to different neurotropic substances (Quesney and Gloor 1978;Stach and Kacz 1977;Hwa and Avoli 1991). On the other hand, epileptiform discharges may normally occur on the normal background of the bioelectric cortical activity (Cavazzuti et al 1980;Guerrini et al 1995) or during anaesthesia (Steriade et al 1993).…”

The role of dopamine in epilepsy

“…Examples include the myoclonic jumping evoked by the administration of a high dose of 5-hydroxytryptophan to guinea pigs (Volkman et al, 1978;Weiner et al, 19791, and the secondarily generalised limbic motor seizures provoked in rats by a large systemic injection of the muscarinic cholinergic agonist pilocarpine (Turski et al, 1988). Focal seizures elicited by the chronic implantation of a cobalt-gelatine pellet (Dow et al, 1974;Farjo and McQueen, 1979) or by topical application of ouabain to the cortex (Stach and Kacz, 1977) are similarly suppressed by apomorphine. So, too, are the seizures induced by the neuroexcitant kynurenic acid (but, interestingly, not quinolinic acid [Lapin and Ryzov, 19901) and the tonic convulsions initiated by the P-carboline derivative DMCM (Sekimoto et al, 1992).…”

“…So, too, are the seizures induced by the neuroexcitant kynurenic acid (but, interestingly, not quinolinic acid [Lapin and Ryzov, 19901) and the tonic convulsions initiated by the P-carboline derivative DMCM (Sekimoto et al, 1992). Apomorphine will also combine synergistically with GABA mimetics to allay seizures (Kleinrok et al, 1981;Stach and Kacz, 1977). Several synthetic aporphines are equally efficacious in suppressing reflex audiogenic seizures in mice (Anlezark et al, 1978(Anlezark et al, ,1981 and photomyoclonus in the baboon (Anlezark et al, 1983).…”