The Cathinones MDPV and α-PVP Elicit Different Behavioral and Molecular Effects Following Acute Exposure

Since the mid-to-late 2000s, synthetic cathinones have gained popularity among drug users due to their psychostimulant effects greater than those produced by cocaine and amphetamine. Among them, 3,4-methylenedioxypyrovalerone (MDPV) and 1-phenyl-2-(pyrrolidin-1-yl)pentan-1-one (alpha-PVP) are ones of the most popular cathinones available in the clandestine market as bath salts or fertilizers. Pre-clinical studies indicate that MDPV and alpha-PVP induced psychomotor stimulation, affected thermoregulation, and promoted reinforcing properties in rodents. However, a direct comparative analysis on the effects caused by MDPV and alpha-PVP on the behavior and neuronal activation in rodents is still lacking. Behavioral analyses revealed that both MDPV and alpha-PVP affect spontaneous and stimulated motor responses. In particular, MDPV showed a greater psychomotor effect than alpha-PVP in line with its higher potency in blocking the dopamine transporter (DAT). Notably, MDPV was found to be more effective than alpha-PVP in facilitating spontaneous locomotion and it displayed a biphasic effect in contrast to the monophasically stimulated locomotion induced by alpha-PVP. In addition to the behavioral results, we also found a different modulation of immediate early genes (IEGs) such as Arc/Arg3.1 and c-Fos in the frontal lobe, striatum, and hippocampus, indicating that these drugs do impact brain homeostasis with changes in neuronal activity that depend on the drug, the brain area analyzed, and the timing after the injection. These results provide the first discrimination between MDPV and alpha-PVP based on behavioral and molecular data that may contribute to explain, at least in part, their toxicity.