Hippocampal histopathological changes after subchronic misuse of Clonazepam and alpha-tocopherol's mitigating role in rats

Background: The Food and Drug Administration (FDA) authorized clonazepam (CZP) in 1976 as an antiepileptic medication to treat a variety of seizures. There is a significant risk of abuse, tolerance, physical dependency, and eventually addiction with clonazepam. The negative effects of clonazepam are negligible, despite several studies confirming the negative effects of other antiepileptics such as carbamazepine and Valproic acid. This study is to evaluate the protective function of alpha-tocopherol, commonly referred to as "vitamin E" (Vit E), as well as the neurotoxic effects of sub chronic high-dose clonazepam administration. Methods: Forty male albino rats in good health were used in the investigation. Four equal groups of ten rats each were randomly assigned to them: group I received normal saline; group II received CZP misuse; group III received vitamin E in corn oil; and group IV received CZP plus vitamin E. For 50 days, all rats were given the prescribed medications. Hippocampal tissues were gathered to examine the gene expression of dopamine receptors and perform immunohistochemical and histological analyses. Results: At the conclusion of the research, the groups that received medication had gained a significant amount of weight. There were more damaged cells and detrimental effects on hippocampus tissues in the group that abused CZP. Also, there was a greater degree of up-regulation of dopamine-2 receptors (D2Rs) and down-regulation of dopamine-1 receptors (D1Rs). Conclusions: Excessive levels of CZP caused neurotoxicity, hippocampus tissue disruption, and an increase in the number of degenerated cells, as well as disturbance in dopamine receptor gene expression. Treatment with alpha-tocopherol considerably reduced the harmful effects caused by CZP.