Agmatine attenuates ethanol withdrawal induced audiogenic seizures in rats

Agmatine signalling plays a pivotal role in the endogenous response to mitigate seizures and associated neurodegeneration. Rats were exposed to varying ethanol concentrations (20 % w/v) for 7 days followed by abrupt withdrawal, coupled with high-frequency sound exposure (92-100 dB, 90 s) to induce audiogenic seizures which are characterized by wild running, myoclonic jerks, and tonic-clonic episodes. Notably, alterations in GABA, glutamate, and pro-inflammatory cytokines were observed in the brain of ethanol-withdrawn rats. The study demonstrated that agmatine administration (40 & 80 mg/kg, i.p.) and other agmatinergic agents such as L-arginine (100 mg/kg, i.p.), aminoguanidine (50 mg/kg, i.p.), and arcaine (25 mg/kg, i.p.) significantly attenuated ethanol withdrawal-induced seizure scores. Furthermore, agmatine and its endogenous modulators effectively lowered increased pro-inflammatory cytokine levels in ethanol-withdrawn rats. Additionally, agmatine was found to decrease elevated glutamate levels and increase GABA levels in ethanol-withdrawn rats. These results emphasize the possible therapeutic usefulness of agmatine as a targeted biological intervention for alcohol withdrawal-induced seizures in rats. By elucidating the intricate molecular mechanisms underlying the induction of seizures during ethanol withdrawal and demonstrating the effectiveness of agmatine in mitigating these seizures, this study contributes to the understanding of neurobiological responses to ethanol withdrawal and suggests novel avenues for therapeutic intervention.