Seizures and wet-dog shakes induced by 4-aminopyridine, and their potentiation by nifedipine.
The behavioral and electrographic effects of 4-aminopyridine (4-AP) administered i.p. or microinjected into the hippocampal CA1 region (i.h.) were studied in rats. The modification of such effects by the systemic administration of the Ca2+ antagonist dihydropyridine, nifedipine, was also studied. 4-AP i.p. (5 mg/kg) induced generalized tonic convulsions in 74% of the animals and death in 13%. Convulsions were characterized by electrical discharges of relatively short duration in all structures studied (frontal cortex, amygdala, dorsal hippocampus and dorsal raphe). Limbic seizures and frequent wet-dog shakes were observed when 4-AP was administered i.h. (2-4 nmol) and this behavior was correlated with hippocampal discharges, which rapidly propagated to the other structures. Pretreatment with nifedipine (7.5-50 mg/kg s.c.) markedly potentiated the effects of 4-AP. The percentage of rats that died during generalized convulsion after i.p. 4-AP increased to 56-87% and the frequency of wet-dog shakes increased after i.h. microinjection of 4-AP. Moreover, nifedipine-treated rats showed long-lasting (greater than 60 min) continuous discharges in all structures studied (status epilepticus). These results are discussed in the light of the possible participation of Ca2+ channels in the convulsant effect of 4-AP and its potentiation by nifedipine.
Fragoso-Veloz
J
J
Departamento de Neurociencias, Universidad Nacional Autónoma de México, D.F.
Massieu
L
L
Alvarado
R
R
Tapia
R
R
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004357:Drug Synergism; D004569:Electroencephalography; D006624:Hippocampus / Q000033:anatomy & histology; D008297:Male; D008845:Microinjections; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D015761:4-Aminopyridine; D009543:Nifedipine