Behavioral and neurochemical alterations after lithium-pilocarpine administration in young and adult rats: a...

Pilocarpine and lithium-pilocarpine can induce seizures and brain damage in adult rats. However, manifestation of cerebral lesions seems to be an age-related phenomenon suggesting that maturational states of neurocircuitry may be involved. We have studied behavior changes, cerebral histopathology, and muscarinic and dopaminergic receptors density in rodents subjected to lithium-pilocarpine treatment. Wistar rats, at two different ages (21 days and 2 months), were treated with pilocarpine (15 mg/kg, SC), lithium (3 mEq/kg, IP), atropine (50 mg/kg, IP) and the combination of lithium to pilocarpine. Histopathologic studies showed that younger animals were more resistant to the development of cerebral changes and there was a preferential involvement of the striatum (Wilcoxon p = 0.02) as opposed to more generalized areas in adult animals such as hippocampus and neocortex. Lithium treatment induced an upregulation of muscarinic receptors at both ages, and this effect was reversed in younger animals after pilocarpine administration. Lithium also induced an upregulation of dopaminergic receptors in the striatum at both ages (p < 0.05), and this effect was not reversed after pilocarpine administration. Our data confirm that young animals show less brain damage after lithium-pilocarpine, and main alterations in dopaminergic receptors density occur in young and older animals after treatment with lithium and lithium combined to a low dose of pilocarpine.