Opposite effects of a GABA(B) antagonist in two models of epileptic seizures in developing rats.
The action of a GABA(B) antagonist CGP 35348 and a GABA(B) agonist baclofen was studied in two models of epileptic seizures characterized by EEG spike-and-wave rhythm in freely moving immature rats. Rhythmic metrazol activity (RMA, model of human absences) was induced by low systemic dose of pentylenetetrazol (PTZ) in 18- and 25-day-old rats, epileptic after discharges (ADs, model of human myoclonic seizures) were elicited by electrical stimulation of sensorimotor cortex in rat pups 12, 18, and 25 days old. CGP 35348 (50, 100 and 200 mg/kg i.p.) suppressed RMA in both age groups in a dose-dependent manner. Simultaneously it increased the incidence of clonic seizures, potentiating thus an effect of PTZ. Baclofen (1, 3 and 6 mg/kg i.p.) augmented markedly RMA in 25-day-old rats. On the contrary, baclofen suppressed RMA in a part of 18-day-old animals. Incidence of seizures was not changed by baclofen in either age group. As ADs are concerned CGP 35348 (100 and 200 mg/kg i.p.) exhibited a proconvulsant action, baclofen (3, 6 or 12 mg/kg i.p.) was anticonvulsant, but again an irregularity of action was found in 18-day-old rats. The role of GABA(B)-mediated inhibition in epileptogenesis depends on the type of seizures and also on the stage of maturation.
Mares
Pavel
P
Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic. maresp@biomed.cas.cz
Slamberová
Romana
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D003292:Convulsants / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003292:Convulsants; D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid