Drug-induced changes in brain acetylcholine.

In rats, drug-induced depression of the central nervous system has been shown generally to be associated with an elevation in level of total acetylcholine in the brain. This generalization held true for a wide variety of depressant drugs with one notable exception: the subacute administration of reserpine, with which there was an increase in cerebral acetylcholine after the first dose, but a return to normal levels after subsequent doses, despite continued depression of the animals. Reduction in the level of total acetylcholine in the brain followed the administration of certain convulsants (pentylenetetrazole and 3,5-dimethylbutylethylbarbiturate); but no change was seen after the administration of several mildly exciting agents. The notable exceptions to this generalization were atropine and scopolamine, which significantly lowered brain acetylcholine in doses producing mild excitation in only some of the animals and no gross manifestations in the rest.