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

Abstract

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 (α-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 α-PVP induced psychomotor stimulation, affected thermoregulation, and promoted reinforcing properties in rodents. However, a direct comparative analysis on the effects caused by MDPV and α-PVP on the behavior and neuronal activation in rodents is still lacking. Behavioral analyses revealed that both MDPV and α-PVP affect spontaneous and stimulated motor responses. In particular, MDPV showed a greater psychomotor effect than α-PVP in line with its higher potency in blocking the dopamine transporter (DAT). Notably, MDPV was found to be more effective than α-PVP in facilitating spontaneous locomotion and it displayed a biphasic effect in contrast to the monophasically stimulated locomotion induced by α-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 α-PVP based on behavioral and molecular data that may contribute to explain, at least in part, their toxicity.

Genotoxic Properties of Synthetic Cannabinoids on TK6 Human Cells by Flow Cytometry

“…The neuropharmacological, neurochemical, and behavioral effects of various substances belonging to the NPS category are well known and widely demonstrated [7,36,37]. Also, with regard to SCBs, recent studies are available aimed at investigating, mainly in vivo, the psychostimulant and neuropharmaco-toxicological effects [23,24,26].…”

Methcathinone and 3-Fluoromethcathinone Stimulate Spontaneous Horizontal Locomotor Activity in Mice and Elevate Extracellular Dopamine and Serotonin Levels in the Mouse Striatum

“…Enhancement of spontaneous locomotor activity in mice observed after treatment with MC and 3-FMC is less potent compared to effects of α-pyrrolidinophenone analogs, such as 3,4-MDPV and α-PVP. Both α-pyrrolidinophenones significantly increased the total distance covered during experiment, even at the dose of 1 mg/kg or 3 mg/kg, while MC and 3-FMC failed to do so at 1 and 3 mg/kg (Giannotti et al 2017; Wojcieszak et al 2018b). Additionally, in various studies, effects of 3,4-MDPV and α-PVP at 10 mg/kg persisted for 120–240 min (Gatch et al 2013, 2015; Giannotti et al 2017, Wojcieszak et al 2018b), while in the current study effects of MC and 3-FMC at the same dose worn out after 60 and 110 min, respectively.…”

“…Both α-pyrrolidinophenones significantly increased the total distance covered during experiment, even at the dose of 1 mg/kg or 3 mg/kg, while MC and 3-FMC failed to do so at 1 and 3 mg/kg (Giannotti et al 2017; Wojcieszak et al 2018b). Additionally, in various studies, effects of 3,4-MDPV and α-PVP at 10 mg/kg persisted for 120–240 min (Gatch et al 2013, 2015; Giannotti et al 2017, Wojcieszak et al 2018b), while in the current study effects of MC and 3-FMC at the same dose worn out after 60 and 110 min, respectively. These observations are in line with the study by Marusich et al (2012), in which the effects of 3-FMC seem to be weaker compared to 3,4-MDPV and tend to terminate before 90 min at doses below 30 mg/kg.…”

The synthetic cathinone psychostimulant α‐PPP antagonizes serotonin 5‐HT2A receptors: In vitro and in vivo evidence

“…Nevertheless, SCs also have distinctive pharmacokinetic profiles, such as long half‐lives and distinctive neuromolecular effects . Furthermore, some SCs interact with targets other than monoamine transporters .…”

“…16 Nevertheless, SCs also have distinctive pharmacokinetic profiles, such as long half-lives 17 and distinctive neuromolecular effects. 18 Furthermore, some SCs interact with targets other than monoamine transporters. 19,20 These properties may also contribute to the psychological and behavioral effects of SCs.…”