Objective: The past ten years have seen an increase in gabapentin (GBP) overuse and abuse in Egypt after pregabalin scheduling. Numerous studies have demonstrated the detrimental effects of pregabalin; nonetheless, GBP`s effects are minimal. The objective of this investigation is to study GBP-induced neurotoxicity in rats and the protective benefits of alpha-tocopherol (vitamin E `Vit E`).

Material and Methods: Forty (40) adult male albino rats were randomly split into four groups: (10 rats each): Group I, which was subdivided into group Ia (5 rats), received a regular diet as a negative control; group Ib (5 rats) received corn oil as a positive control; group II received alpha-tocopherol; group III (GBP misuse); and group IV received GBP + alpha-tocopherol. The corresponding medicines were administered to every rat for fifty days. Neurobehavioral tests were performed on the day of scarification. Hippocampal tissues were collected for immunohistochemical and histological analysis.

Results: Weight gain rose considerably by the end of the research in the drug-treated groups. In neurobehavioral tests, controls performed better and had higher locomotor indices. The group that misused GBP showed more deteriorated cells and more negative effects on hippocampal tissues. These histological alterations dramatically decreased with alpha-tocopherol therapy.

Conclusion: GBP in high doses had neurotoxic effects, disrupted hippocampal tissues, and increased the number of degenerated cells. Alpha-tocopherol treatment significantly attenuated the deleterious effects induced by GBP.