Studies Related to the Cholinergic Influence on the Accumulation and Disappearance of Monoamines in Rat Brain

The influence of atropine, hemicholinium base No. 3 (HC-3), and physostigmine on the changes produced in the cerebral levels of monoamines by pargyline, α-methyl-p-tyrosine (α-MT), and reserpine was investigated in rats. The results disclosed that atropine and HC-3 decreased both the accumulation of dopamine (DA) after monoamine oxidase inhibition with pargyline and its disappearance after tyrosine hydroxylase inhibition with α-MT. Both drugs caused an increase of noradrenaline (NA) disappearance after α-MT but neither affected the accumulation of NA after pargyline. In contrast, physostigmine inhibited the loss of NA and accentuated that of DA. HC-3 markedly inhibited the accumulation of serotonin (5-HT) while other drugs exhibited no significant effect. Choline partly antagonized the action of HC-3 on DA and 5-HT accumulation. The neuroleptic haloperidol increased the α-MT-induced loss of catecholamines. Atropine and HC-3 partially blocked the haloperidol–α-MT effect on DA levels but increased the effect on NA levels. Physostigmine had effects opposite to those of atropine or HC-3 in haloperidol–α-MT-treated rats. Reserpine-induced depletion of catecholamines or their subsequent recovery was not affected by any of the test drugs. Pargyline afforded considerable protection against the in vivo toxicity of HC-3 in mice, while it potentiated the lethal effects of choline and physostigmine.