Impact of levetiracetam and ethanol on memory, selected neurotransmitter levels, oxidative stress parameters, and essential elements in rats

• Published in: Pharmacological reports 2024-12, Vol.76 (6), p.1363-1376
• Main Authors: Zwierzyńska, Ewa, Klimczak, Michał, Nasiadek, Marzenna, Stragierowicz, Joanna, Pietrzak, Bogusława
• Format: Article
• Language: English
• Subjects: Animals; Brain - drug effects; Brain - metabolism; Drug Safety and Pharmacovigilance; Ethanol - pharmacology; Glutamic Acid - metabolism; Levetiracetam - pharmacology; Male; Medicine; Memory - drug effects; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - metabolism; Neurotransmitter Agents - metabolism; Oxidative Stress - drug effects; Pharmacotherapy; Pharmacy; Rats; Rats, Wistar; Spatial Memory - drug effects
• ISSN: 1734-1140; 2299-5684; 2299-5684
• DOI: 10.1007/s43440-024-00659-5

Background Ethanol disrupts brain activity and memory. There is evidence supporting the beneficial effect of levetiracetam on alcohol consumption. Therefore, the aim of the study was to examine whether levetiracetam has a protective activity against ethanol-induced memory impairment, alterations in selected neurotransmission activities, oxidative stress, and selected essential elements in rats. Methods The rats were given levetiracetam (300 mg/kg b.w. po ) with ethanol for three weeks prior to behavioral tests. Spatial memory was tested using the Morris water maze, while recognition memory was evaluated using the Novel object recognition test. The GABA and glutamate concentration was determined in three rat brain regions (cerebellum, hippocampus, and cerebral cortex). Serum oxidative stress parameters and selected essential elements concentration (Cu, Mn, Zn, Fe, Mg) in the rat brain were analyzed. Results Levetiracetam administered with ethanol improved spatial memory, but did not affect abstinence-induced impairment. The drug also decreased ethanol-induced long-term recognition memory impairment. No alterations in glutamate levels were observed. GABA levels were elevated by levetiracetam in the cerebral cortex and by ethanol in the cerebellum. Ethanol increased catalase activity (CAT) and decreased superoxide dismutase activity (SOD) in the serum. Levetiracetam significantly increased the activity of SOD. Alcohol disrupted the levels of trace elements (Mn, Zn, Mg) in the rat brain. Additionally, levetiracetam alone increased Mg, Fe, and Cu concentrations while all animals receiving the drug also had significantly lower concentrations of Zn. Conclusions Levetiracetam had differential effects against ethanol-induced impairments. These findings could have important implications for future levetiracetam treatment in patients.