REPEATED TOLUENE EXPOSURE EXACERBATES MOTOR RESPONSES IN A MURINE MODEL OF PARKINSON’S DISEASE

Parkinson’s disease (PD) is a neurodegenerative disorder of multifactorial etiology involving genetic and environmental factors. Among these, exposure to solvents like toluene has been linked to neurodegenerative damage; however, evidence has largely focused on occupational exposure, while the effects of intense, short term exposure patterns, such as those associated with drug abuse, remain underexplored. This study assessed the effects of repeated toluene exposure in a murine model of MPP⁺ induced PD, focusing on motor deficits and dopaminergic neurodegeneration. A dose response curve was first performed to identify a sub-effective dose of MPP⁺. With this approach, mice received intrastriatal injections of MPP⁺ or saline and were exposed to toluene (0 or 2000 ppm, twice daily for 7 days). Motor coordination was assessed by the rotarod test (latency to first fall and number of falls), forelimb strength and endurance were evaluated using the wire hanging test; and apomorphine induced rotational behavior was assessed to evaluate nigrostriatal dopaminergic function. In a separate group, striatal dopamine and its metabolites (DOPAC and HVA) were quantified using high-performance liquid chromatography (HPLC). Exposure to toluene or MPP⁺ alone impaired motor performance, while combined exposure exacerbated these deficits; toluene reduced hanging times, and combined treatment produced control-like responses, and apomorphine-induced rotations showed an additive effect, suggesting greater nigrostriatal damage. Neurochemical analysis showed altered DOPAC levels without changes in dopamine or HVA. Overall, repeated toluene exposure exacerbated MPP⁺-induced motor deficits and may affect dopaminergic homeostasis, highlighting organic solvent abuse as a risk factor for Parkinson-like motor alterations.