Evaluation of the effects of new antiepileptic drug, AMPA receptor antagonist – Perampanel on neurotoxicity of dexamethasone – Behavioral study
INTRODUCTION: The long-term treatment with glucocorticoids (GCs) and other preparations, e.g. dexamethasone (DEX – a synthetic GCs receptor agonist) or prolonged stress and elevated levels of endogenous corticosteroids are frequently associated with psychosis as well as with cognitive deficits, such as the impairment of memory and learning. GCs potentiate stress or ischemia-induced accumulation of excitatory amino acids (EAA) in the extracellular space of hippocampus. The antagonism of glutamate receptors may potentially play a role in the safe therapy with glucocorticoids. AIM(S): The purpose of this study was to investigate the effect of perampanel (Fycompa – a new antiepileptic drug, non‑competitive α‑amino‑3‑hydroxy‑5‑methyl‑4‑isoxazolepropionate (AMPA) receptor antagonist) in animal model of dexamethasone-induced neurotoxicity. METHOD(S): The experiments were carried out on male Albino Swiss mice (25-30 g). Perampanel, at the dose of 4, 6, 10 or 12 mg/kg/day, was administered ip, 30 min before DEX (16 mg/kg/day, ip), for 14 days. The long-term memory acquisition, the motor performance, the locomotor activity, as well as the body weight and the lethality were evaluated after 14 days of drugs administration. RESULTS: The results of the study have shown that DEX evoked deterioration of all parameters in behavioral tests. At the doses of 4 or 6 mg/kg/day, perampanel administered in mice treated with DEX, had no significant effect on the parameters of the motor performance and the locomotor activity tests, although it degraded the long-term memory acquisition. However, when administered at the dose of 10 mg/kg/day (but not at the dose of 12 mg/kg/day), perampanel slightly improved acquisition of memory, but it had no impact on other behavioral parameters in mice subjected to DEX for 14 days. CONCLUSIONS: The above findings suggest that treatment with perampanel at higher doses (10 mg/kg/day) could prevent the neurotoxic effects induced by DEX, but further study needs to be carried out to explain this effect. FINANCIAL SUPPORT: Supported by the grant from the Medical University of Lublin, No DS 449.