The effects of manganese on the cholinergic receptor in vivo and in vitro may be mediated through modulation of free radicals.

Incubation of rat brain tissue in the presence of catecholamine autoxidation products catalysed by manganese led to a dose-dependent decrease in high-affinity binding of 3H-QNB. Such effects may be due to receptor destruction or inactivation through membrane damage mediated by free radicals or cytotoxic quinones arising from the powerful in vitro effects in catalysing dopamine autoxidation. In contrast, administration of manganese to neonatal rats for fourteen days resulted in an increase in 3H-QNB binding in the striatum but not in other brain regions. Inhibition of lipid peroxidation by manganese treatment was also most pronounced in the striatum. Thus, manganese can display remarkable dichotomy in acting both as pro-oxidant or powerful antioxidant. The prevailing state may be dictated under pathological conditions by the redox status of a particular region of brain as well as by the amount of manganese deposited there. Under physiological conditions endogenous manganese may subserve a neuromodulatory role in specific neural areas related to control of redox bioenergetics.