Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference

Duart-Castells, Leticia; Blanco-Gandía, M. Carmen; Ferrer-Pérez, Carmen; Puster, Brigitte; Piccoli, David A.; Miñarro, José; Escubedo, Elena; Rodrı́guez-Arias, Marta

doi:10.1016/j.pnpbp.2020.109876

Cited by 11 publications

(10 citation statements)

References 72 publications

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“…Taken together, these data suggest that, except in rare cases, CBD does not affect the rewarding effects of psychostimulants. Moreover, CBD modulation of the CPP paradigm is highly dependent on the psychostimulant used, as supported by previous studies highlighting the behavioural and molecular differences between cocaine and MDPV (Duart-Castells et al, 2020, 2019a, 2019b.…”

Section: Discussionsupporting

confidence: 65%

“…Previous research has evidenced that the MDPV-induced CPP at doses similar to that used in this study in both rats (King et al, 2015) and mice (Duart-Castells et al, 2020).…”

Section: Discussionsupporting

confidence: 54%

“…Consistent with this mechanism of action, some authors found that MDPV has powerful rewarding effects measured by ultrasonic vocalizations in rats in the self-administration paradigm (Simmons et al, 2018(Simmons et al, , 2017. In the same line, MDPV-induced rewarding effects in the conditioned place preference (CPP) in mice (Duart-Castells et al, 2020) and rats (Hicks et al, 2018;Risca et al, 2020).…”

Section: Highlightsmentioning

confidence: 71%

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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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Section: Discussionsupporting

confidence: 65%

“…Previous research has evidenced that the MDPV-induced CPP at doses similar to that used in this study in both rats (King et al, 2015) and mice (Duart-Castells et al, 2020).…”

Section: Discussionsupporting

confidence: 54%

Section: Highlightsmentioning

confidence: 71%

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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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“…Despite numerous studies describing the reinforcing and discriminative stimulus effects of MDPV, 4,5,12,19–22 little is known about relapse‐related effects of MDPV, 23,24 and nothing is known about how these effects might be altered by common bath salts constituents, such as caffeine. Although MDPV (1 mg/kg) can reinstate responding in the presence or absence of infusion‐paired stimuli, 23 other factors (e.g., priming dose and self‐administration history) that mediate the magnitude of the reinstatement response have yet to be explored.…”

Section: Introductionmentioning

confidence: 99%

Interactions between reinforcement history and drug‐primed reinstatement: Studies with MDPV and mixtures of MDPV and caffeine

Doyle

Sulima²,

Rice³

et al. 2020

Addiction Biology

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Many drugs of abuse are mixed with other psychoactive substances (e.g., caffeine) prior to their sale or use. Synthetic cathinones (e.g., 3,4‐methylenedioxypyrovalerone [MDPV]) are commonly mixed with caffeine or other cathinones (e.g., 3,4‐methylenedioxy‐N‐methylcathinone [methylone]), and these “bath salts” mixtures (e.g., MDPV + caffeine) can exhibit supra‐additive interactions with regard to their reinforcing and discriminative stimulus properties. However, little is known about relapse‐related effects of drug mixtures. In these studies, male Sprague–Dawley rats self‐administered 0.032 mg/kg/inf MDPV or a mixture of MDPV + caffeine (0.029 + 0.66 mg/kg/inf, respectively) and then underwent multiple rounds of extinction and reinstatement testing to evaluate the influence of reinforcement history and drug‐associated stimuli on the effectiveness of saline (drug‐paired stimuli alone), MDPV (0.032–1.0 mg/kg), caffeine (1.0–32 mg/kg), and mixtures of MDPV:caffeine (in 3:1, 1:1, and 1:3 ratios, relative to each drug's ED50) to reinstate responding. Dose‐addition analyses were used to determine the nature of the drug–drug interaction for each mixture. MDPV and caffeine dose‐dependently reinstated responding and were equally effective, regardless of reinforcement history. Most fixed ratio mixtures of MDPV + caffeine exhibited supra‐additive interactions, reinstating responding to levels greater than was observed with caffeine and/or MDPV alone. Drug‐associated stimuli also played a key role in reinstating responding, especially for caffeine. Together, these results demonstrate that the composition of drug mixtures can impact relapse‐related effects of drug mixtures, and “bath salts” mixtures (MDPV + caffeine) may be more effective at promoting relapse‐related behaviors than the constituents alone. Further research is needed to determine how other polysubstance reinforcement histories can impact relapse‐related behaviors.

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“…MDPV high lipophilicity may be held responsible for its enhanced blood–brain barrier (BBB) permeability [ 2 , 3 ] and drug brain levels [ 5 ], hence contributing to its potency at DAT and, therefore, to the dose-dependent increase of extracellular dopamine (DA) in the nucleus accumbens (NAc), often associated with locomotor and rewarding effects [ 7 , 12 , 13 ]. MDPV has been mostly studied for its psychostimulant features with abuse potential [ 6 ], namely the locomotor activity [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], self-administration behavior [ 14 , 19 , 21 , 22 ], conditioned place preference [ 20 , 23 ], and drug discrimination [ 14 , 17 , 24 ] parameters. Undoubtedly, this synthetic cathinone acts as a potent CNS stimulant, which raises obvious concerns about its potential neurotoxic effects, and possibly amphetamine-like effects, due to their structural similarity.…”

Section: Introductionmentioning

confidence: 99%

Acute MDPV Binge Paradigm on Mice Emotional Behavior and Glial Signature

et al. 2021

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3,4-Methylenedioxypyrovalerone (MDPV), a widely available synthetic cathinone, is a popular substitute for classical controlled drugs of abuse, such as methamphetamine (METH). Although MDPV poses public health risks, its neuropharmacological profile remains poorly explored. This study aimed to provide evidence on that direction. Accordingly, C57BL/6J mice were exposed to a binge MDPV or METH regimen (four intraperitoneal injections every 2 h, 10 mg/kg). Locomotor, exploratory, and emotional behavior, in addition to striatal neurotoxicity and glial signature, were assessed within 18–24 h, a known time-window encompassing classical amphetamine dopaminergic neurotoxicity. MDPV resulted in unchanged locomotor activity (open field test) and emotional behavior (elevated plus maze, splash test, tail suspension test). Additionally, striatal TH (METH neurotoxicity hallmark), Iba-1 (microglia), GFAP (astrocyte), RAGE, and TLR2/4/7 (immune modulators) protein densities remained unchanged after MDPV-exposure. Expectedly, and in sheer contrast with MDPV, METH resulted in decrease general locomotor activity paralleled by a significant striatal TH depletion, astrogliosis, and microglia arborization alterations (Sholl analysis). This comparative study newly highlights that binge MDPV-exposure comes without evident behavioral, neurochemical, and glial changes at a time-point where METH-induced striatal neurotoxicity is clearly evident. Nevertheless, neuropharmacological MDPV signature needs further profiling at different time-points, regimens, and brain regions.

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Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference

Cited by 11 publications

References 72 publications

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

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

Interactions between reinforcement history and drug‐primed reinstatement: Studies with MDPV and mixtures of MDPV and caffeine

Acute MDPV Binge Paradigm on Mice Emotional Behavior and Glial Signature

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