Hyperglycemia-related neuropathy leads to the onset and exacerbation of several pathologies. The C. elegans model has been used to study this phenomenon and its underlying mechanisms using a broad evaluation for neurodegeneration. Here, we report a system-specific susceptibility for glucotoxicity, namely the dopaminergic, glutamatergic and cholinergic system. Under high-glucose conditions, these systems (and not the serotonergic or GABAergic) were impaired, as observed by evaluating the fluorescent signal in GFP-tagged worm strains. The significance and implications of unequal susceptibility for glucotoxicity in the nervous system is discussed.