Colchicine lesions in the rat hippocampus mimic the alterations of several markers in Alzheimer's disease.

An infusion of colchicine into the hippocampi of rats resulted in destruction of hippocampal cells. Twelve days after infusion, preoperative trained colchicine-treated rats showed a significant decrease in choice accuracy in a T-maze learning task. There was also local reduction in choline acetyltransferase (ChAT) activity and significant losses of 55-kDa protein in the soluble fraction and of 50-kDa protein in myelin and synaptosomal fractions in the hippocampi of colchicine-lesioned rats. There was a marked increase in [3H]glutamate binding in the hippocampus and cortex. In contrast, [3H]quinuclidinyl benzilate binding in the hippocampus was slightly reduced, whereas [3H]dihydroalprenolol binding was not affected by the colchicine treatment. Scatchard analysis revealed that the increase in glutamate binding is due to an increase in the number of glutamate receptors without significant change in their affinity. Some of the changes caused by hippocampal infusion of colchicine resemble those seen in Alzheimer's disease suggesting the use of such rats as one model for the disease.