The impact of modafinil on memory and brain oxidative stress: contrasting effects of acute and chronic administration in healthy rats

Metab Brain Dis. 2025 Apr 24;40(5):191. doi: 10.1007/s11011-025-01600-2.

ABSTRACT

The present study assessed the impact of modafinil (MD) on memory function and oxidative damage in the brains of naive rats. Wistar rats were administered either a single dose or repeated doses (over 30 days) of water or MD (75, 150, or 300 mg/kg) via gavage. The novel object recognition (NOR), open-field habituation (OFH), and inhibitory avoidance task (IA) tested the animals’ memory. Furthermore, the oxidative and nitrosative stress markers (4-hydroxynonenal [4-HNE], 8-isoprostane [8-ISO], 3-nitrotyrosine [3-nitro], superoxide dismutase [SOD], and catalase [CAT]) were assessed in the frontal cortex, hippocampus and striatum of the rats. The acute administration of MD did not affect any memory measures or oxidative stress parameters evaluated in this study. In contrast, chronic MD administration at a dose of 300 mg/kg decreased memory related to habituation and recognition. In addition, chronic administration of this drug increased oxidative lipid damage, evaluated through 8-ISO and 4-HNE. These findings suggest a potential link between chronic MD use, memory impairment, and oxidative stress in the brains of rats, emphasizing the importance of further research in this area.

PMID:40272613 | DOI:10.1007/s11011-025-01600-2