Neurotoxic effects of combined exposure to caffeine and pyrethroids in mice

Abstract

Introduction and Objective. Pyrethroids are manufactured insecticides known for their neurotoxicity, which can cause seizures, impairment of cognitive and motor functions. Caffeine (CAF), a nonselective adenosine A1 and A2A receptor antagonist and commonly used psychoactive substance, may affect these disorders in a dose-dependent manner. The aim of the study was to determine the neurotoxic potential of co-exposure to pyrethroids and CAF in mice. Materials and method. CAF in combination with deltamethrin (DEL), β-cyfluthrin (CYF) or tefluthrin (TEF) was evaluated against pyrethroid-induced seizures, as well as in the passive avoidance task and rotarod test for the assessment of learning and motor coordination, respectively. All substances were administered acutely by intraperitoneal injections and CAF was used at doses capable of interfering with pharmacological activities of other compounds. Results. The CD50 value for each pyrethroid (median pyrethroid convulsive dose causing seizures in 50% of mice was unaffected by CAF (40 mg/kg). Pyrethroids at their 1/5 CD50 did not impair learning, whether administered alone or with CAF. In the rotarod test, CAF (40 mg/kg) potentiated the harmful impact of TEF (2.3 mg/kg) on motor coordination, while having no effect on two other pyrethroids. TEF (2.3 mg/kg) alone and in combination with CAF (40 mg/kg), reduced acetylcholinesterase (AChE) activity in the brain at comparable levels. Conclusions. This study demonstrates that TEF neurotoxicity may be increased in the presence of CAF co-exposure. The interaction of TEF and CAF with the cholinergic system, resulting in a decrease in AChE activity in the brain, is not responsible for the effect observed in the rotarod.