7,8-Dihydroxyflavone blocks the development of behavioral sensitization to MDPV, but not to cocaine: Differential role of the BDNF-TrkB pathway

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

doi:10.1016/j.bcp.2019.02.004

Cited by 10 publications

(11 citation statements)

References 59 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%

“…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%

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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%

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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“…First, CBD, at other doses or different treatment schedules, could have resulted in different outcomes among the groups. Second, MDPV differs from the psychostimulants mentioned above in its potency and targets within the brain [ 4 , 7 , 54 ] as well as in its behavioural and cognitive effects [ 8 , 45 ]. Therefore, it is reasonable to consider that the interactions between CBD and MDPV are different from the 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

IJMS

View full text Add to dashboard Cite

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 paradigms. In addition, we assessed the effects of the co-administration 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. Furthermore, CBD exerted anxiolytic-like effects, exclusively in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice varies depending on the requirements of the learning task, resulting in a complex response. Therefore, further research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

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“…On the test day, horizontal locomotor activity (HLA) was measured as described by (Duart-Castells et al, 2019), with minor modifications. Briefly, the animals were given their corresponding i.p.…”

Section: Horizontal Locomotor Activity (Hla)mentioning

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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7,8-Dihydroxyflavone blocks the development of behavioral sensitization to MDPV, but not to cocaine: Differential role of the BDNF-TrkB pathway

Cited by 10 publications

References 59 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

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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