Studies on the behavioral and biochemical effects of hemicholinium in vivo.

The commonly accepted mechanism of action of HC-3, i.e., an inhibition of high affinity Ch uptake at the cholinergic nerve terminal appears to provide a satisfactory explanation of its effects in vivo.

Abstract

Hemicholinium (HC-3) causes a behavioral reactivity in rats which is correlated with the depletion of brain acetylcholine (ACh). The decrease in ACh levels and behavioral effects caused by HC-3 are correlated in a dose-dependent manner, maximal effects being achieved at an intraventricular (i.vt.) dose of 1 microgram. The HC-3 concentration in the brain 2 hr after i.vt. injection does not increase further with doses greater than 10 microgram. HC-3 (i.vt.) does not affect the uptake of choline (Ch) into subcellular fractions prepared from treated animals. ACh depletion in the brain areas studied closely parallels the HC-3 distribution. HC-3 pretreatment results in greater effects on newly synthesized than on stored ACh. Utilizing a concentration equal to that found in brain after an in vivo dose, HC-3 does not inhibit the uptake of Ch in synaptosomal preparations in which the neuronal membrane was disrupted with ether. The commonly accepted mechanism of action of HC-3, i.e., an inhibition of high affinity Ch uptake at the cholinergic nerve terminal, appears to provide a satisfactory explanation of its effects in vivo.