Age-dependent anticonvulsant action of clonazepam in the N-methyl-D-aspartate model of seizures.
Seizures may result from an impaired balance between excitation and inhibition. We tested whether clonazepam [a benzodiazepine that enhances GABAA inhibitory transmission (0.2 or 1.0 mg/kg, intraperitoneally [i.p.])] suppresses an age-dependent pattern of N-methyl-D-aspartate (NMDA)-induced phenomena in 7-, 12-, 18-, 25-, and 60-day-old rats (10, 40, 100, 100, and 200 mg/kg of NMDA, i.p., respectively). There were no effects of clonazepam against the NMDA-induced automatisms and emprosthotonus. In 7-day-old rats, clonazepam was proconvulsant in clonic-tonic seizures (it decreased the latency to onset of seizures, whereas it was anticonvulsant in 25-day-old rats. There was no difference between anticonvulsant effects of clonazepam and its solvent in 12- and 60-day-old rats. Both cortical and hippocampal EEG seizures was extremely poor in this model. There was no improvement of EEG recording after clonazepam. The results demonstrate that impaired excitation cannot be simply balanced by an enhanced inhibition and that the drug effects in young animals cannot be predicted from the effects in adults.
Velísek
L
L
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Mareś
P
P
D000375:Aging / Q000502:physiology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002998:Clonazepam / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000517:prevention & control / Q000523:psychology; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology
D000927:Anticonvulsants; D002998:Clonazepam; D016202:N-Methylaspartate