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.
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Abbreviations
- α-PVP:
-
1-Phenyl-2-(pyrrolidin-1-yl)pentan-1-one
- MDPV:
-
3,4-Methylenedioxypyrovalerone
- DA:
-
Dopamine
- DAT:
-
Dopamine transporter
- IEGs:
-
Immediately early genes
- NE:
-
Norepinephrine
- 5-HT:
-
Serotonin
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Experimental protocols performed in the present study were in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the European Communities Council Directive of September 2010 (2010/63/EU) and were approved by Italian Ministry of Health (license no. 335/2016-PR) and by the Ethics Committee of the University of Ferrara.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in the studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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This research has been funded by the Drug Policies Department; Presidency of the Council of Ministers, Italy (project NS-Drugs to M. Marti) by local funds from the University of Ferrara (FAR 2016 to M. Marti); by FIRB 2012 from the Italian Ministry of the University (Grant no. RBFR12LDOW to F. De Giorgio; Institute of Public Health, Section of Legal Medicine, Catholic University of Rome, Italy); and the Zardi Gori Foundation (Zardi Gori Grant to F. Fumagalli).
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Giannotti, G., Canazza, I., Caffino, L. et al. The Cathinones MDPV and α-PVP Elicit Different Behavioral and Molecular Effects Following Acute Exposure. Neurotox Res 32, 594–602 (2017). https://doi.org/10.1007/s12640-017-9769-y
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DOI: https://doi.org/10.1007/s12640-017-9769-y