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Seizures and wet-dog shakes induced by 4-aminopyridine, and their potentiation by nifedipine

1990; Elsevier BV; Volume: 178; Issue: 3 Linguagem: Inglês

10.1016/0014-2999(90)90106-g

1879-0712

Jorge Fragoso-Veloz, Lourdes Massieu, Raúl Alvarado, Ricardo Tapia,

Pharmacological Receptor Mechanisms and Effects

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 discharge, 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 (> 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.