Biochemical and ultra-structural studies of the effect of alprazolam as an anxiolytic drug on the cerebellum of adult male mice

In the recent decade, there has been increasing concern on the hazard effect of drugs on different species. Stressful life events contribute to the development of many neurodegenerative and neuropsychiatric disorders including depression and anxiety. Alprazolam (ALP) is commonly used and approved for the medical treatment of panic and anxiety disorders, such as generalized anxiety or social anxiety disorders. Thus, it was of a particular interest to investigate the effect of ALP on the neurons of cerebellar cortex of mice, where mice have genomic similarities to human. So, biochemical, histological and ultrastructural investigations are reported on the cerebellum of adult male mice subjected to three different doses of ALP, for two months. These doses were equivalent to the human therapeutic doses as 0.5, 1 and 1.5 mg. In a dose dependant manner, significant decreases in the levels of both acetylcholine enzyme activities and total glutathione are recorded, indicating that the activity of acetylcholine esterase was inhibited by free radical formation. Little histopathological changes were observed in the cerebellar cortex of mice administered with 0.5 mg ALP. Marked alterations were observed in the Purkinje neurons of cerebellar cortex of mice administered with 1 and 1.5 mg ALP, where unstained haloes are seen around most of these cells. Their nuclei were eccentrically placed, and pyknotic. The intracellular structure of Purkinje cells showed dilatation of both rER and Golgi apparatus. Many small vesicles near the Golgi bodies were accumulated to form clusters, probably indicate disturbance in the vesicular transport between rER and Golgi apparatus. These results reflect the injured effect of high dose ALP on brain activity, performing in the possible ultrastructural abnormalities as well as its oxidative stress.