Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine

López-Arnau, Raúl; Duart-Castells, Leticia; Aster, Barbara; Camarasa, Jorge; Escubedo, Elena; Piccoli, David A.

doi:10.1007/s00213-018-5052-z

Cited by 20 publications

(24 citation statements)

References 62 publications

(82 reference statements)

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“…Our results are in line with previous findings demonstrating that psychostimulant effects of 3,4-MDPV are long-lasting. This can be seen in molecular studies, as the blockade of DA re-uptake was more persistent after 3,4-MDPV than in the case of cocaine, a model stimulant [29], and in animal models, where locomotor stimulation induced by 3,4-MDPV had a longer duration compared to cocaine and methamphetamine [17].…”

Section: Discussionmentioning

confidence: 95%

“…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: 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: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

et al. 2020

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“…Second, MDPV differs from the psychostimulants above mentioned in its potency and targets within the brain (Baumann et al, 2017;Lopez-Arnau et al, 2019;Simmler et al, 2012) and its behavioural and cognitive effects (Baumann et al, 2013;Duart-Castells et al, 2019b). Therefore, it might be reasonable to consider that the interactions between CBD and MDPV are different from interactions with other psychostimulants.…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

Alegre-Zurano

López-Arnau

Luján

et al. 2021

Preprint

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3,4-methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the “bath salts”. Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigm. We also assessed the effects of the combination of CBD, and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Additionally, CBD exerted anxiolytic-like effects, but only in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice vary depending on the requirements of the learning task, resulting in a complex response. More research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

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“…For the synaptosomal preparation, male Sprague-Dawley rats (Janvier, Le Genest, France) weighing 225-250 g (2-3 months-old) were used. This rat strain has been used widely to obtain pure rat brain synaptosomes (Kolanos et al, 2015;Gannon et al, 2018;Lopez-Arnau et al, 2019;Saha et al, 2019). The animals were housed in temperature-controlled conditions (22 ± 1°C) under a 12 h light/dark cycle and had free access to food (standard laboratory diet, Panlab SL, Barcelona, Spain) and drinking water.…”

Section: Subjectsmentioning

confidence: 99%

Role of amino terminal substitutions in the pharmacological, rewarding and psychostimulant profiles of novel synthetic cathinones

Duart-Castells¹,

Muralter²,

Nadal-Gratacós³

et al. 2020

Preprint

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Background and Purpose: The emergence of new synthetic cathinones continues to be a matter of public health concern. In fact, they are quickly replaced by new structurally related alternatives. The main goal of the present study was to characterize the pharmacological profile, the psychostimulant and rewarding properties of novel synthetic cathinones differing in its amino terminal substitution. Experimental Approach: Rat brain synaptosomes were used for [3H]dopamine uptake experiments. HEK293 transfected cells (hDAT, hSERT, hOCT; human dopamine, serotonin and organic cation transporter, respectively) were also used for [3H]monoamine uptake and transporter binding assays. Molecular docking allowed to investigate the effect of the amino substitutions on the biological activity. Locomotor activity experiments and conditioned place preference paradigm were used in order to study the psychostimulant and rewarding effects in mice. Key Results: All compounds tested are potent inhibitors of DAT with very low affinity for SERT, hOCT-2 and -3, and their potency inhibiting DAT increased when the aminosubstituent expanded from a methyl-to either an ethyl-, a pyrrolidine-or a piperidine-ring. Regarding the in vivo results, all the compounds induced an increase in locomotor activity and possess rewarding properties. Results also showed a significant correlation between predicted binding affinities by molecular docking and affinity constants (Ki) for hDAT. Conclusions and Implications: Our study demonstrated the role of the amino-substituent in the pharmacological profile of novel synthetic cathinones and provides the first evidence that some of them are potent DAT inhibitors and able to induce psychostimulant and rewarding effects in mice.

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Effects of MDPV on dopamine transporter regulation in male rats. Comparison with cocaine

Cited by 20 publications

References 62 publications

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

Comparative neuropharmacological studies on three pyrrolidine-containing synthetic cathinones

Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

Role of amino terminal substitutions in the pharmacological, rewarding and psychostimulant profiles of novel synthetic cathinones

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