Intracerebroventricular administration of ethylcholine mustard aziridinium ion (AF64A) reduces release of acetylcholine from rat hippocampal slices

Abstract

Ethylcholine mustard aziridinium ion (AF64A), or vehicle, was infused bilaterally (3 nmol/3 μl per side) into the lateral ventricles of rats. The effect of such treatment on various cholinergic responses was measured in the hippocampus, cortex and striatum. Potassium-stimulated release of acetylcholine from superfused slices of hippocampus was reduced, 7 and 21 days after treatment with AF64A, to 24 and 35% of control, respectively. The activity of choline acetyltransferase in the hippocampus also decreased, to 42% of control, both 7 and 21 days after treatment with AF64A. Similarly, the activity of acetylcholinesterase and the high affinity transport of choline in the hippocampus were reduced, to 40 and 30% of control; and to 33 and 48% of control, respectively, 7 and 21 days after treatment with AF64A. Synthesis of acetylcholine in slices of hippocampus was also decreased after treatment with AF64A (71 and 51% of control, 7 and 21 days post-AF64A respectively). Only the binding of [ 3h]qnb in the hippocampus was unchanged at 7 days after treatment with AF64A, although a small reduction (11%) was noted 21 days after treatment with AF64A. The activity of choline acetyltransferase and acetylcholinesterase, the high-affinity transport of choline and the binding of fhiqnb in cortex and striatum were unaffected by treatment with AF64A under the same experimental conditions. Using a substantially smaler dose than that earlier reported in mice, the earlier finding was thus confirmed, and extended, in rats, of a highly selective effect of AF64A on several components of the cholinergic system. Under the conditions of this study, these effects appeared to be confined to the hippocampus.