EFFECTS OF BILATERAL CHOLINOTOXIN INFUSIONS ON THE BEHAVIOR AND BRAINBIOCHEMISTRY OF THE RATS

We examined behavioral and biochemical specificity and the general use fulness of the proposed rat model of Alzheimer's disease. Bilateral in fusions of ethylcholine aziridinium (AF64A) into the basal magnocellul ar nuclei caused a deterioration of learning in passive and active avo idance tests, increased emotional reactivity, and decreased motoric ac tivity. Choline acetyltransferase activity was decreased by 22% in the frontal cortex but increased by 8-10% in the hippocampus and hypothal amus. Noradrenaline and dopamine levels in the frontal cortex were dec reased by 20%. In striatum, dopamine and its metabolites were strongly suppressed (by 50-60%). Also striatal noradrenaline (-48%) and 5-hydr oxytryptamine (-34%) were significantly decreased. Hypothalamic 5-hydr oxytryptamine was increased (+25%). Bilateral AF64A lesions decreased significantly (by 14-20%) activities of prolyl endopeptidase, dipeptid yl peptidase II and IV in hippocampal and frontal cortical brain homog enates. These results show that AF64A can be used to induce long-term learning deficits in the rat. However, striatal amine levels are also strongly suppressed, and are reflected as hypomotility and increased e motional reactivity. These changes may limit the usefulness of the rat model. Universally decreased peptidase activities offer interesting v iews regarding the role of peptidase inhibitors in amnestic disorders.