Cannabinoid Type 1 Receptor Antagonist Impaired Spatial Memory and Increased the Tau Gene Expression in Animal Model of the Alzheimer's disease

Tavakoli-Far, Bahareh; Zeraati, Maryam; Choopani, Samira; Falah, Parviz; Darabi, Parisa; Mazloom, Roham; Bayat, Gholamreza; Hosseini, Marjan; Goudarzvand, Mahdi

doi:10.32592/ARI.2024.79.5.935

Cannabinoid Type 1 Receptor Antagonist Impaired Spatial Memory and Increased the Tau Gene Expression in Animal Model of the Alzheimer's disease

Document Type : Original Articles

Authors

¹ Department of Physiology and Pharmacology, Alborz University of Medical Sciences Karaj, Iran

² Department of physiology and Pharmacology, Pasteur Institute, Tehran, Iran

³ Alborz University of Medical Sciences

10.32592/ARI.2024.79.5.935

Abstract

Alzheimer's disease is a neurodegenerative disease characterized by the accumulation of two different proteins, β-amyloid and tau. The present study aimed to scrutinize the effects of bilateral administration of the cannabinoid receptor antagonist (AM251) in the hippocampus on spatial memory and tau gene expression in an Alzheimer's disease model. β-amyloid toxin was injected bilaterally into the hippocampus of Wistar male rats to induce Alzheimer's disease, and the rats were then categorized into the control group (receiving distilled water as β-amyloid toxin solvent), lesion group (receiving β-amyloid toxin), β-amyloid + DMSO group (as antagonist solvent of AM251), and AM251 antagonist receiving groups (5, 25, and 100 ng). During the training course of the Morris water maze test, the antagonist of the cannabinoid 1 receptor AM251 was injected bilaterally into the hippocampus for four days at doses of 5, 25, and 100 ng. To assess the spatial memory of the animals, the parameters of the distance traveled by the animals, latency time to reach the hidden platform, velocity of the animals, and tau gene expression in real time were analyzed.
The spatial memory indices were impaired after injection of β-amyloid and AM251 cannabinoid antagonist. The mRNA expression of tau protein increased following the injection of β-amyloid toxin, but there was no significant difference between the cannabinoid antagonist and β-amyloid groups.
These results indicate the destructive effect of beta-amyloid toxin on spatial memory, as well as the positive role of the cannabinoid system in memory formation and consolidation, although further studies are warranted in this regard.

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