Additive Effects of Streptozotocin and Aluminum Chloride on Cognitive Decline and Brain Damage in Rats: A Behavioral and Histopathological

Background: Streptozotocin (STZ) and Aluminum Chloride (AlCl₃) are recognized neurotoxins implicated in models of cognitive decline and neurodegeneration. This study investigated the comparative effects of STZ, AlCl₃, and their combination on cognitive performance and brain structural integrity. Methods: Cognitive function was assessed using the T-maze test, and structural damage was evaluated through histopathological examination of brain tissue across four groups: Control, STZ-treated, AlCl₃-treated, and Combination-treated. Results: All three treatment groups showed significant cognitive impairment and histopathological changes compared to the Control group. In the T-maze test, the Combination group exhibited the maximum degree of cognitive impairment, showing a significantly greater deficit than either the STZ or AlCl₃ groups alone. In contrast, histopathological assessment revealed that the magnitude of cellular and structural impairment was comparable across the STZ, AlCl₃, and Combination groups, though all were significantly different from the Control. Conclusion: Co-exposure to STZ and AlCl₃ leads to a marked synergistic or additive effect on behavioral neurotoxicity, resulting in maximal cognitive deficits. However, the histopathological evidence suggests that the individual agents (STZ or AlCl₃) may already induce a comparable level of maximal structural damage, indicating a dissociation between the severity of morphological and functional impairment under these experimental conditions.