Δ9-THC Administration Reduces Microtubule Protein Network Dynamics and Impairs Memory Formation in Male Wistar Rats

Abstract Background There is growing evidence of microtubule dynamics in memory formation and learning. Dynamic microtubules are involved in dendritic spine changes, synaptic plasticity, axonal transportation, and cell polarity. Besides, one of the well-studied effects of cannabis on human behavior is memory disability. As Δ9-tetrahydrocannabinol (∆9-THC) is the most crucial ingredient of cannabis, we investigated the effect of ∆9-THC on memory function by treating rats and conveying a behavioral study. Results Our results show the poor performance of THC-treated animals in T-maze compared to the control group. Results of the turbidity assay demonstrate that ∆9-THC reduces microtubule polymerization in a concentration-dependent manner. Circular Dichroism spectroscopy also studied structural changes of purified tubulin, which revealed the significant changes in the secondary structure of tubulin. Furthermore, in silico studies predicted one binding site for ∆9-THC on β-tubulin. Conclusions We concluded that ∆9-THC can reduce the stability of the microtubule, and this may conversely affect synaptic plasticity, thus learning and memory. We proposed that brain function is affected by microtubule dynamic changes caused by the secondary structural changes of tubulin and preventing tubulin-tubulin interaction.