Effects of intracerebroventricular AF64A administration on cholinergic, serotoninergic and catecholaminergic circuitry in rat dorsal hippocampus.

Five nmol ethylcholine mustard aziridinium ion, a potential cholinotoxin was administered bilaterally into the cerebral ventricles of male rats at coordinates A -1.5, L +/- 1.5 and V -4.0 mm. The dorsal hippocampi were processed for choline acetyltransferase, serotonin or tyrosine hydroxylase immunocytochemistry 7 days after the injection to determine the specificity of the effect of the drug. Intrinsic choline acetyltransferase positive cells were also found after treatment, while the overall staining of fibres decreased. No change was observed in staining for either serotonin or tyrosine hydroxylase. Using the electron microscope, degenerating nerve terminals, with recognizable synaptic specializations were encountered, most frequently in stratum oriens and occasionally, degenerated CA3 pyramidal cells were observed. These findings are consistent with the neurochemical data obtained in parallel experiments with the morphological study in which it was found that acetylcholine content of the hippocampus was reduced by 73.4% 7 days after ethylcholine mustard aziridinium ion treatment, while dopamine, noradrenaline and serotonin levels were unaffected. Furthermore, the morphological studies indicate that ethylcholine mustard aziridinium ion can exert selective effects on the cholinergic system of dorsal hippocampus without significantly altering its cytoarchitecture.