Characterization of lithium potentiation of pilocarpine-induced status epilepticus in rats

Subcutaneous administration of pilocarpine to rats that were pretreated with a small dose of lithium chloride results in the evolution of generalized convulsive status epilepticus. The production of status epilepticus is absolutely reproducible, has a very consistent time to onset (22 min), has a duration of several hours, and is extremely severe with a high mortality rate. Experimental results show that this animal model of status epilepticus: (i) requires activation of muscarinic receptors because the initiation of seizures is blocked by atropine; (ii) requires presynaptic cholinergic activity because it is attenuated by hemicholinium-3; (iii) recruits noncholinergic cells because when status epilepticus is established it is not altered by atropine administration; and (iv) is blocked by pretreatment with diazepam and ongoing seizures are terminated by administration of diazepam, similar to certain forms of status epilepticus in humans. The reproducibility, prolonged nature, and involvement of a clearly defined neurochemical system as the triggering mechanism, i.e., cholinergic activation, makes this a potentially valuable animal model of generalized convulsive status epilepticus.