Actions of Atropine, Hemicholinium-3, and Physostigmine on Chlorpromazine-Induced Changes in Rat Brain Monoamines

The influence of atropine, hemicholinium-3 (HC-3), and physostigmine on the accumulation of monoamines after monoamine oxidase inhibition with pargyline, and on their disappearance after synthesis inhibition with α-methyl-p-tyrosine (α-MT), was investigated in whole brain of normal and chlorpromazine (CPZ)-treated rats. The results disclosed that the accumulation of dopamine (DA) and serotonin (5-HT) is significantly inhibited by atropine and HC-3, as is the loss of DA. None of these drugs affected the noradrenaline (NA) accumulation except for HC-3, which produced a small but statistically significant potentiation. Both atropine and HC-3 increased while physostigmine inhibited the disappearance of NA. These drugs, however, had no effect on the normal cerebral concentrations of monoamines. CPZ substantially increased the accumulation of DA and 5-HT and the loss of DA and NA without affecting their normal concentrations. HC-3, and to some extent atropine, inhibited the action of CPZ on the accumulation of DA and 5-HT. These drugs also inhibited the CPZ-induced accentuation of DA loss but enhanced that of NA. Physostigmine produced the opposite effects. In both normal and CPZ-treated animals, choline, which by itself was ineffective, partly reversed the actions of HC-3 but not that of atropine. These results support the hypothesis of cholinergic–aminergic interaction at the cerebral level and demonstrate the usefulness of HC-3 as a tool in such investigations.