Cholinergic rebound after chlorpromazine exacerbates lithium muscarinic-induced limbic seizures in rats: implications for psychiatric treatment.

When lithium serum levels were within the (human) therapeutic range, young and old adult male and female rats (housed singly or in groups) all displayed faster limbic seizure onset times in response to a muscarinic cholinergic agonist (pilocarpine 20 mg/kg) if a single systemic dosage of chlorpromazine was injected 24 hours previously. The effect was comparable to injecting an additional 10 mg/kg of pilocarpine. These results strongly suggest that cholinergic rebound from chlorpromazine administrations during lithium treatment could facilitate subclinical electrical lability and very localized neuronal necrosis within the limbic system of clinical patients, resulting in normalization of psychiatric symptoms.