When fish take a bath: Psychopharmacological characterization of the effects of a synthetic cathinone bath salt 'flakka' on adult zebrafish.

Alpha-pyrrolidinopentiophenone (α-PVP) is a synthetic cathinone which exerts robust mental and physiological effects clinically, as well as causes aberrant stereotypic behaviors and altered locomotion in rodents. Given the rich spectrum of pharmacological activity of α-PVP in rodents and humans, as well as its high abuse potential, further studies are needed to better understand the pharmacology and toxicology of this drug. The zebrafish (Danio rerio) is a relatively novel model organism in neuropharmacology and toxicology research. Here, we characterize behavioral effects of α-PVP in adult zebrafish following its acute (1, 5, 25 and 50 mg/L for 20 min) and chronic (1, 5 and 10 mg/L for 7 days) treatments. Overall, acute exposure to α-PVP evoked psychostimulant (but not anxiolytic-like) effects in zebrafish novel tank test, with characteristic stereotypic 'side-to-side' bottom swimming at 5, 25 and 50 mg/L. The high-performance liquid chromatography/high-resolution mass spectrometry (HPLC/HRMS) analyses of zebrafish brains showed detectable levels of α-PVP following its acute administration, likely underlying the observed behavioral effects. Although acute 2-day discontinuation of chronic 7-day α-PVP at 1, 5 and 10 mg/L produced no effects, hypolocomotion occurred after a 7-day chronic treatment and repeated withdrawal, resembling rodent effects of some chronic psychostimulants. Collectively, these findings support zebrafish sensitivity to α-PVP and show some parallels with its effects in mammals and humans. This study also suggests that aquatic models based on zebrafish can help further examine the CNS effects evoked by α-PVP and screen for related synthetic new psychoactive drugs.