Studies on the behavioral and biochemical effects of hemicholinium in vivo.
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.
D000109:Acetylcholine / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006426:Hemicholinium 3 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D006426:Hemicholinium 3; D002794:Choline; D000109:Acetylcholine