Background and Objectives: Study of deleterious effect of neurotoxins on the animals' brain is a fascinating research plan. In this project, the damage effect of colchicine on the hippocampal cornu ammonis 1 (CA1) was examined by the studying the hippocampal tissue. Materials and Methods: Injections of colchicine (1-75 μg/rat, intra- hippocampal CA1) were performed in cannulated male Wistar rats while being settled in the stereotaxic apparatus. Control group was solely injected saline (1 μl/rat, intra-CA1). Other groups of rats were trained in the conditioning device to receive the colchicine (5 and 25 µg/rat, intra- CA1) prior to the testing; the control group was given saline (1 µl/rat, intra-CA1). At the end of the experiments, the rats were decapitated and their brains were removed for histological studies. Results: The number of the small pyramidal cells of hippocampal CA1 showed a decrease in the colchicine-received rats than the control group. The novelty behavioral assessment showed a significant difference between the colchicine given rats versus control (pConclusion: Hippocampal CA1 layer plays an important role in the memory and learning processes. Lesion of this region by the aid of neurotoxins (e.g. colchicines) may lead us to provide a proper animal model to study the learning dysfunctions in the future. This research may appropriately validate the lesion effect of the toxin in the hippocampal CA1. It may also propose an incidence of the novelty seeking behavior due to the lesion in the hippocampus.