Piperazine designer drugs elicit neurotoxicity in the alternative in vivo model Caenorhabditis elegans

Abstract

Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1-benzylpiperazine (BZP), 1-(4-methoxyphenyl)piperazine (MeOPP), and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). Generally, they can be consumed as capsules, tablets, but also in powder or liquid forms. Although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the neurotoxic effects of BZP, MeOPP and MDBP using C. elegans as in vivo model through acute toxicity, development, reproduction, and behavior tests. The LD50 for BZP, MeOPP e MDBP was 52.21, 5.72, and 1.22 mM respectively. All concentrations were accompanied by a significant decrease in the body surface of the worms, indicating alteration of the development and decrease in reproduction. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed though the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters (DATs). In summary, we suggest that piperazine designer drugs leads to neuronal damage, which might be the underlying cause of altered behavior.