Studies on the role of brain cholinergic systems in the therapeutic mechanisms and adverse effects of ECT and lithium.

Brain cholinergic systems are thought to play an important role in memory function and mood regulation. Electroconvulsive therapy (ECT) and lithium (Li) have substantial therapeutic effects on abnormal mood and may adversely affect cognitive processes. The effects of chronic electroconvulsive shock (ECS) and Li administration on brain muscarinic cholinergic receptors (MCR), and on functional correlates of altered brain cholinergic activity, were therefore studied. ECS reduced MCR number in the cerebral cortex and diminished cataleptic responses to the muscarinic agonist, pilocarpine. MCR down-regulation may have therapeutic implications in depression which has been putatively linked to central cholinergic supersensitivity. Alternatively, ECS effects on brain cholinergic function may be involved in the pathogenesis of ECT-induced memory deficits. Both ECS-induced MCR subsensitivity and a clinically equivalent model of ECT-induced anterograde amnesia were not demonstrable after a single ECS, were cumulatively induced by repeated treatments, and may be reversible by administration concurrently with ECS of a muscarinic antagonist. Li increased MCR binding marginally in the cortex and hippocampus and significantly in the corpus striatum. Li substantially enhanced cataleptic and hypothermic responses to pilocarpine. Combined Li-scopolamine pretreatment had an additive effect on these cholinergically mediated responses. Effects of Li and scopolamine on MCR binding were not additive, a finding supporting the conclusion that Li enhances brain cholinergic function by its presynaptic effects on acetylcholine turnover and release. Possible implications for the therapeutic mechanisms and adverse effects of Li are considered.