Contradictory effects of GABA-B receptor agonists on cortical epileptic afterdischarges in immature rats

Abstract

Classical GABA-B receptor agonist baclofen exhibits anticonvulsant as well as proconvulsant effects and these effects change during postnatal development. Epileptic afterdischarges (ADs) elicited by stimulation of sensorimotor cortex were used to analyze if it is a specific feature of baclofen or if another agonist SKF97541 possesses the same properties. To study developmental point of view 12-, 18- and 25-day-old rats were used. Both agonists exhibited anticonvulsant (decreased intensity of motor phenomena) and proconvulsant (decreased threshold intensities necessary for transition of epileptic activity into limbic structures; prolongation of ADs) action and these actions changed with age. SKF97541 is much more potent than baclofen. In addition to similarities marked differences between the two drugs were found. SKF97541 was able to increase threshold intensities of stimulation current necessary for elicitation of movements directly bound to stimulation, spike-and-wave type of ADs and accompanying clonic seizures in 12- and 18-day-old rats, baclofen was without effect. Suppression of intensity of both motor phenomena (movements and clonic seizures) was marked with SKF97541 in 12- and 18-day-old rats; this effect was only marginal in baclofen-treated animals. We can speculate that different subsets of GABA-B receptors are influenced by the two agonists but further studies are necessary.