Effect of central stimulants and depressants on mouse brain acetylcholine and choline levels

Brain concentrations of acetylcholine and choline were measured within 5-30 min after an i.p. injection of central stimulant or depressant drugs. The acetylcholine concentration in whole mouse brain of controls was 2.35 ± 0.06 μg/g wet wt. (16.1 nmol/g wet wt.) while the choline concentration was 6.52 ± 0.21 μg/g wet wt. (62.7 nmol/g). Physostigmine, 0.5 mg/kg, oxotremorine, 2 mg/kg free base, and haloperidol, 4 and 8 mg/kg, increased both acetylcholine and choline 20 min after administration. Pentobarbital, 55 mg/kg, and diazepam, 5-40 mg/kg, increased only acetylcholine without affecting choline. Atropine, 50 mg/kg, lowered acetylcholine without affecting choline. Haloperidol, 1 mg/kg, chlorpromazine, 10 mg/kg, reserpine, 2.5 mg/kg, 20 hr, desmethylimipramine, 20 mg/kg, and amphetamine, 7 and 15 mg/kg, had no effect on either acetylcholine or choline. No drug studied caused a simultaneous decrease in these two quaternary amines. The possible significance of these findings on the mechanism of action of these drugs is discussed.