Effects of a GABA-B receptor agonist baclofen on cortical epileptic afterdischarges in rats.

Abstract

Inhibition mediated by GABA-B receptors can play a role in epilepsy. We therefore studied its involvement in cortical epileptic afterdischarges in adult rats by means of a GABA-B receptor agonist baclofen. Three different experiments were performed with cortical epileptic afterdischarges and an additional experiment studied possible effect of baclofen on cortical interhemispheric (transcallosal) evoked potentials. Baclofen was administered intraperitoneally in doses of 3 or 6 mg/kg. In contrast to a marked proconvulsant action of a GABA-B receptor antagonist baclofen did not exhibit clear anticonvulsant action against EEG afterdischarges but a moderate effect on motor phenomena was observed. On the contrary, it tended to decrease threshold intensities for individual epileptic phenomena. Augmentation of postictal refractoriness by baclofen was found only with a short poststimulation interval (2 min). Cortical interhemispheric responses induced by single pulses were influenced only moderately by baclofen; paired-pulse potentiation induced by short intervals between stimuli was not changed but there was a depression of the second response induced 200 and 250 ms after the first one with the 6 mg/kg dose of baclofen. Failure of baclofen to exhibit an expected anticonvulsant activity might be due to a complexity of GABA-B inhibitory system (pre- as well as postsynaptic localization of GABA-B receptors).

• Authors: Pavel Mares, Jirí Lindovský, Romana Slamberová, Hana Kubová
• Journal: Epileptic disorders : international epilepsy journal with videotape (Epileptic Disord) Vol. 9 Suppl 1 Pg. S44-51 (Dec 2007) ISSN: 1294-9361 [Print] United States
• PMID: 18319200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GABA Agonists
• Receptors, GABA-B
• Baclofen

Topics

• Animals
• Baclofen (pharmacology, therapeutic use)
• Cerebral Cortex (drug effects, physiopathology)
• GABA Agonists (pharmacology, therapeutic use)
• Male
• Rats
• Receptors, GABA-B (drug effects)
• Seizures (drug therapy, physiopathology)
• Severity of Illness Index
• Treatment Failure