Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure

Allen, Serena; Tran, Lily; Oakes, Hannah; Brown, Russell W.; Pond, Brooks B.

doi:10.1007/s12640-019-00020-2

Cited by 8 publications

(8 citation statements)

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“…Moreover, 3,4-MDPV fully substitutes for cocaine and methamphetamine in rodents trained to discriminate these drugs from saline, which confirms its reinforcing effects and points to the similarity in the mechanisms of action between 3,4-MDPV and classic psychostimulants [17]. Intermittent administration of 3,4-MDPV in rodents leads to the sensitization to its stimulant effects [12,14,15,20], which is a feature related to the drugs' addictive properties [27], and can be explained by the induction of adaptational changes in dopamine (DA) neurotransmission, such as changes in the DAT activity, or changes in density of D 1 -and D 2 -DA receptors [28][29][30].…”

Section: Introductionsupporting

confidence: 56%

“…The drug has been found to increase spontaneous locomotor activity in rats and mice, an effect involving stimulation of D 1 -dopamine receptors. As in a case of other psychostimulants, acute effects of 3,4-MDPV administration are dose-dependent and follow an inverted U-shaped curve, meaning that low and medium doses induce increase of locomotion, while higher doses result in suppression of locomotor activity, mainly due to the occurrence of intense stereotypies, such as licking, gnawing, grooming, sniffing and self-injurious behaviors [6,8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. In line with the high ability to potentiate dopaminergic neurotransmission, 3,4-MDPV is endowed by rewarding and reinforcing properties, as it induces conditioned place preference [8,14,24,25], lowers thresholds for intracranial self-stimulation [23,26] and is self-administered by rodents [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

et al. 2020

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Purpose 3,4-Methylenedioxypyrovalerone (3,4-MDPV) is a prevalent member of α-pyrrolidinophenones, a group of new psychoactive substances, known for its strong psychostimulant effect resulting from potent stimulation of dopamine (DA) circuitry in the brain. As 3,4-MDPV and its derivatives are successively being scheduled, each year novel analogs appear on the market. This study aimed at examination and direct comparison of psychostimulant properties of structural isomer of 3,4-MDPV, namely 2,3-MDPV along with a model α-pyrrolidinophenone, pyrovalerone. Methods Open field spontaneous locomotor activity of mice was assessed as a measure of psychostimulant potency. To evaluate the in vivo pharmacological properties of the drugs, extracellular levels of DA and serotonin (5-HT) in the mouse striatum were measured using an in vivo microdialysis technique followed by high-performance liquid chromatography with electrochemical detection. Involvement of dopaminergic system in the behavioral effects of the tested α-pyrrolidinophenones was examined by pre-treatment with a selective D 1-DA receptor antagonist, SCH 23390, before measurement of locomotor activity in response to the drugs. Results 3,4-MDPV, 2,3-MDPV and pyrovalerone produced time-and dose-dependent stimulation of locomotor activity, with 3,4-MDPV being more potent than the other two compounds. Observed locomotor stimulation was mediated by elevated DA-ergic neurotransmission, as all compounds caused a significant increase of extracellular DA levels in the striatum, with 3,4-MDPV being the most potent, and psychostimulant effects were abolished by SCH 23390. Interestingly, the tested pyrovalerones caused in vivo elevation of extracellular 5-HT levels, which contrasted with their in vitro pharmacologic properties. Conclusions Pyrovalerone, 2,3-MDPV and 3,4-MDPV produced psychostimulant effects mediated by stimulation of dopaminergic neurotransmission. Additionally, all tested compounds elevated extracellular levels of 5-HT in vivo.

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Section: Introductionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

et al. 2020

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“…After i.p. injections of methylenedioxypyrovalerone, mephedrone, and methylone in mice, Allen et al detected an increase of dopamine levels in the substantia nigra and ventral tegumental areas [ 73 ]. Kamińska et al found an increase of extracellular serotonin levels in nucleus accumbens and frontal cortex and that the ingestion of repeated doses of mephedrone in adolescent mice caused single and double-stranded DNA breaks in the frontal cortex in adulthood [ 65 , 74 ].…”

Section: Resultsmentioning

confidence: 99%

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

Daziani

Faro

Montana

et al. 2023

IJMS

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According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances’ cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.

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“…These results are in line with other published data on properties of synthetic cathinones. Behavioral sensitization occurs in laboratory rodents in response to MDPV, mephedrone, and methylone after 6 or 7 days of treatment (Allen et al 2019;Berquist et al 2016;Gregg et al 2013;Kohler et al 2018).…”

Section: Discussionmentioning

confidence: 99%

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

2021

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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.

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Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure

Cited by 8 publications

References 64 publications

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review

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

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