Histochemical and Electronmicroscopic Study of the Brain of the AF64A-Treated Rat

Abstract

It has recently been demonstrated by biochemical means (12,14,17) that ethylcholine aziridinium ion, AF64A (1,12,17), injected intracerebro- ventricularly (i.e.v.), (12), intrastriatally (i.s.) (18,19,20) or intra- hippocampally (i.h.), (14) reduces high affinity choline transport (HAChT), choline acetyltransferase (ChAT) activity, and acetylcholine (ACh) levels in the hippocampus, and to a lesser extent in the striatum, but it does not affect the number of muscarinic acetylcholine-receptors (mAChR-s) (1,2). It has been suggested that AF64A is a neurotoxin which destroys the cholinergic axon terminals and can therefore be considered a “cholinotoxin1”. However, Levy et al. (11) and Jarrard et al. (6) injected AF64A into the substantia nigra or i.e.v., and concluded that AF64A affects other axons besides the cholinergic ones: They thus have cast doubt on the usefulness of AF64A for the specific destruction of cholinergic axon terminals. Since neither Fisher et al. (2) nor Levy et al. (11) presented detailed morphological evidence to support their views, we have decided to conduct our own histochemical and histological studies, including detailed electronmicroscopic investigations. In this paper evidence is given that AF64A is a neurotoxin, and that it can be used as a cholino- toxin if it is administered in the appropriate dose and concentration, at a suitable site of application. Some of these findings have been presented earlier (8,22).