The seizures induced by pilocarpine: behavioral, electroencephalographic and neuropathological studies in rodents

Seizures produced by systemic administration of pilocarpine hydrochloride, a cholinergic muscarinic agonist, in rodents are proposed as a useful animal model of epilepsy. Pilocarpine-induced seizures in rats and mice are characterized by sequential development of behavioral and electrographic signs, which are followed by widespread damage to the forebrain (hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra). Spontaneous seizures may be observed in the long-term period following the administration of convulsant doses of pilocarpine. In experiments designed to examine neuronal networks engaged in the generation and spread of pilocarpine-induced convulsions, a marked role for the basal ganglia is demonstrated. The caudate-putamen, the substantia nigra and the entopeduncular nucleus were found to govern the propagation of seizures produced by pilocarpine. The antiepileptic potential of drugs (diazepam, clonazepam, phenobarbital, valproic acid and trimethadione) against pilocarpine-induced convulsions correlates with their depressant action on the spontaneous activity of non-dopaminergic cells in the substantia nigra. Developmental studies show age-dependent differences in the convulsant response of rats to pilocarpine and status epilepticus are first noted in 2-3 week-old rats, but there is no clear-cut correlation between seizures and evolution of brain damage at this age. The adult pattern of the damage to forebrain is seen after a delay of 1-2 weeks relative to the development of seizures and status epilepticus. The research on the pilocarpine model of convulsions and other cholinergically mediated seizure syndromes may be of value for designing new therapeutic approaches to epilepsy in.