A Cannabinoid Type 1 Receptor Antagonist Impairs Spatial Memory and Increases the Tau Gene Expression in an Animal Model of the Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disease that is characterized by the accumulation of two different proteins, β-amyloid and tau. The objective of the present study was to examine the impact 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. The β-amyloid toxin was administered bilaterally into the hippocampus of Wistar male rats to induce Alzheimer's disease. The rats were then divided into four groups: the control group (which received distilled water as a solvent for β-amyloid toxin), the lesion group (which received the β-amyloid), β-amyloid + DMSO group (as antagonist solvent), and the AM251 antagonist receiving groups. During the training course of the Morris water maze test, the antagonist of the cannabinoid 1 receptor antagonist AM251 was administered bilaterally into the hippocampus for four consecutive days at doses of 5, 25, and 100 ng. To evaluate the spatial memory of the animals, the following parameters were analyzed: distance traveled, latency time to reach the hidden platform, velocity of the animals, and tau gene expression in real time. The spatial memory indices were found to be impaired following the injection of β-amyloid and the AM251 cannabinoid antagonist. Following the injection of β-amyloid toxin, there was an increase in mRNA expression of tau protein. However, no significant difference was observed between the cannabinoid antagonist and β-amyloid groups. These results indicate that β-amyloid toxin has a destructive effect on spatial memory and that cannabinoid system plays a positive role in memory formation and consolidation, However, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]