THE HISTOPATHOLOGICAL, BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF INTRAVENTRICULAR-INJECTION OF ETHYLCHOLINE MUSTARD AZIRIDINIUM (AF64A) IN THE NEONATAL RAT

This study investigated the histopathological, behavioral and neurochemical effects of bilateral injection of 2.0, 0.5 and 0.1 nmol/ventricle ethylcholine aziridinium (AF64A) on postnatal day (PND) 2. The rats showed a significant, but non-dose-related reduction of choline acetyltransferase (ChAT) in the hippocampus but not the cerebral cortex or the caudate nucleus when sacrificed on PND 16. No effect on ChAT was found in any region at PND 58. The group given 2 nmol/ventricle were hyperactive and showed a deficit in spatial learning when tested on the Morris water maze at PND 38-43. No such differences were observed for the rats injected with 0.1 or 0.5 nmol/ventricle AF64A. This spatial learning impairment in the 2 nmol group was associated with non-specific tissue damage seen only in animals from this group that were sacrificed at PND 40. This tissue damage was most evident in the left medial frontal cortex, the caudate nuclei and the anterior dorsal hippocampus.