Effect of oxotremorine on endogenous acetylcholine and on uptake and biotransformation of radioactive choline in discrete regions of mouse brain in vivo

Abstract

Oxotremorine (1 mg/kg) was injected intraperitoneally 15 min before an intravenous dose of 15 nmoles of tritium-labelled choline ([ 3H]choline). The animals were sacrificed 1 or 5 min later by dislocation of the spine. Hypothermia was prevented by a heating lamp. The brains were rapidly dissected into six well-defined regions (cerebellum, medulla oblongata, midbrain, striatum, hippocampus and cortex). Endogenous acetylcholine was significantly (P < 0.01) increased in the striatum (+87%), hippocampus (+49%) and cortex (+115%) but unchanged in the cerebellum, medulla oblongata and midbrain. Pretreatment with methylatropine (5 mg/kg) and with atropine (5 mg/kg) partly counteracted the increase of endogenous acetylcholine in the cortex, and atropine also had the same effect in the striatum. The biosynthesis of [ 3H]acetylcholine at 1 and 5 min was decreased in all regions except the striatum. This was prevented by pretreatment with atropine (5 mg/kg); methylatropine (5 mg/kg) was considerably less effective. In the striatum the formation of [ 3H]acetylcholine was increased (+74–101%) after administration of oxotremorine. The increase was not antagonized by pretreatment with atropine (5 mg/kg) or methylatropine (5 mg/kg). Oxotremorine produced a marked decrease in the specific radioactivities of acetylcholine in the hippocampus and cortex but not in the striatum.