Behavioral Effects of 4-CMC and 4-MeO-PVP in DBA/2J Mice After Acute and Intermittent Administration and Following Withdrawal from Intermittent 14-Day Treatment

Abstract

Synthetic cathinones appeared on the market in the 2000s as new psychoactive substances and gained significant prevalence among drug abusers. Cathinones produce psychostimulant and empathogenic effects by enhancing dopaminergic, noradrenergic, and serotoninergic neurotransmission in the brain, and those which potently and selectively enhance dopaminergic transmission are considered to have higher abuse potential. The present study examines the behavioral effects related to psychostimulant properties, abuse potential, and addiction in DBA/2J mice of two cathinones with different profile of action on monoamine system, 4-chloromethcathinone (4-CMC), and 4-methoxy-pyrrolidinopentiophenone (4-MeO-PVP). 4-CMC and 4-MeO-PVP increase spontaneous locomotor activity after acute treatment and produce behavioral sensitization after 7-day intermittent treatment, which is a common feature of drugs of abuse. 4-MeO-PVP, but not 4-CMC, produces conditioned place preference after 4 days, indicating its rewarding properties. Finally, the ability of 4-CMC and 4-MeO-PVP to induce withdrawal symptoms after discontinuation from 14-day treatment was assessed using a battery of tests for behavioral markers of depression in mice: a tail suspension test, a forced swim test, measuring despair, and a sucrose preference test, measuring anhedonia. None of the three tests revealed increased depressive symptoms. Moreover, neither spontaneous locomotor activity nor motor performance on a rotarod was impaired after 14-day treatment with the tested compounds. These results indicate that 14-day treatment of mice with 4-CMC or 4-MeO-PVP does not induce significant withdrawal symptoms after cessation, nor significant impairment of dopaminergic circuitry resulting in motor impairment. The current study shows that 4-CMC and 4-MeO-PVP produce abuse-related behavioral changes in mice, which are more pronounced after more dopamine-selective 4-MeO-PVP.

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

“…In conclusion, it was confirmed that the effect on locomotory activity is common across different types of synthetic cathinones [ 23 , 30 , 33 , 36 , 41 , 42 , 57 , 59 , 60 , 61 , 62 ].…”

The Addictive and Neurotoxicological Evaluation of Cannabis sativa, male Carica papaya, Nicotiana tabacum and Datura stramonium Alkaloid Extracts via Neuroinflammatory, Neurotransmitter and Oxidative Systems

“…In understanding the neurobiology of addiction and neuropharmacological action of psychoactive plants, CPP model is established to evaluate the reinforcing abilities of a psychoactive substance-paired paradigm against a psychoactive substance-free paradigm (Möller et al, 2018;Wojcieszak et al, 2021). The CCP paradigm is principled on the theory that a textual stimulus can attain secondary appetitive ability when paired with a primary reinforcer, thus indicating abuse liability (Aguilar et al, 2009;Strekalova, 2022).…”

Neurochemical and Cardiovascular Effects of 4-Chloro Ring-Substituted Synthetic Cathinones in Rats

“…4-CMC also affects intracranial selfstimulation (ICSS) in rats (Bonano et al, 2015) in a manner that suggests potential for abuse. Wojcieszak et al (2020Wojcieszak et al ( , 2021 reported that 4-CMC increases locomotor activity in mice, but does not engender conditioned place preference (CPP), a measure of potential rewarding effects. 4-CMC is reported to have toxic effects (Luethi et al, 2019;Zhou et al 2020) and has been detected in samples taken from human drugged driving cases and overdose autopsies (Tomczak et al 2018).…”