Age-specific effects of baclofen on pentylenetetrazol-induced seizures in developing rats.
OBJECTIVE
To determine whether seizures have age-specific features, we studied the role of gamma-aminobutyric acidB (GABAB) transmission in rats of various ages (9, 15, 30, and 60 postnatal days).


METHODS
We used a GABAB receptor agonist baclofen (2 or 5 mg/kg intraperitoneally, i.p.) and a GABAB receptor antagonist CGP 35348 (100 or 600 mg/kg i.p.) in the pentylenetetrazol (PTZ)-induced model of clonic and tonic-clonic seizures (100 mg/kg subcutaneously, s.c.).


RESULTS
Whereas baclofen was anticonvulsant and CGP 35348 proconvulsant in most animals, there were distinct age-related differences in the effectiveness of these drugs and the antagonist had some anticonvulsant activity in adults. Furthermore, the two drugs acting at GABAB receptors had a different profile of action in clonic seizures as compared with tonic-clonic seizures.


CONCLUSIONS
The differences in the age-specific action of the GABAB agonist and antagonist suggest the different GABAB receptor subsets may mediate the drug effects. The results indicate that putative antiepileptic drugs (AEDs) must be tested during development because it may not be possible to extrapolate age-specific anticonvulsant effects from studies in adult animals.
Velísková
J
J
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY USA.
Velísek
L
L
Moshé
S L
SL
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced; D018756:GABA Antagonists / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D009943:Organophosphorus Compounds; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D001418:Baclofen; D010433:Pentylenetetrazole