Exposure of adolescent mice to 3,4‐methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood

López-Arnau, Raúl; Luján, Miguel Ángel; Duart-Castells, Leticia; Piccoli, David A.; Camarasa, Jorge; Valverde, Olga; Escubedo, Elena

doi:10.1111/bph.13771

Cited by 21 publications

(19 citation statements)

References 56 publications

(65 reference statements)

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“…In this sense, our results suggest that there is a high probability that the repeated treatment with MDPV also causes a structural modification of these neuronal elements. As previously reported (López-Arnau et al, 2017), repeated exposure of adolescent mice to MDPV increases ΔFosB expression in the VS 24 h after ending the treatment (≈ 290%) and, although it declined during the 21 days of withdrawal, this factor remained increased (≈ 135%). Additionally, we measured ΔFosB in OFC, because a relationship between its overexpression in this brain area and an increase in risk-taking behavior and locomotor sensitization to cocaine has been demonstrated (Winstanley et al, 2009).…”

Section: Discussionsupporting

confidence: 79%

Neuroadaptive changes and behavioral effects after a sensitization regime of MDPV

et al. 2019

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3,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with cocaine-like properties. In a previous work, we exposed adolescent mice to MDPV, finding sensitization to cocaine effects, and a higher vulnerability to cocaine abuse in adulthood. Here we sought to determine if such MDPV schedule induces additional behavioral-neuronal changes that could explain such results. After MDPV treatment (1.5 mg•kg-1 , twice daily, 7 days), mice were behaviorally tested. Also, we investigated protein changes in various brain regions MDPV induced aggressiveness and anxiety, but also contributed to a faster habituation to the open field. This feature co-occurred with an induction of ΔFosB in the orbitofrontal cortex that was higher than its expression in the ventral striatum. Early after treatment, D2R:D1R ratio pointed to a preponderance of D1R but, upon withdrawal, the ratio recovered. Increased expression of Arc, CDK5 and TH, and decrease in DAT protein levels persisted longer after withdrawal, pointing to a neuroplastic lasting effect similar to that involved in cocaine addiction. The implication of the hyperdopaminergic condition in the MDPV-induced aggressiveness cannot be ruled out. We also found an initial oxidative effect of MDPV, without glial activation. Moreover, although initially the dopaminergic signal induced by MDPV resulted in increased ΔFosB, we did not observe any change in NFκB or GluA2 expression. Finally, the changes observed after MDPV treatment could not be explained according to the autoregulatory loop between ΔFosB and the epigenetic repressor G9a described for cocaine. This provides new knowledge about the neuroadaptive changes involved in the vulnerability to psychostimulant addiction. *Manuscript Click here to view linked References W2, 2 days after the end of the treatment; W3, 3 days after the end of the treatment; W21, 21 days after the end of the treatment, is the end of the withdrawal.

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Section: Discussionsupporting

confidence: 79%

Neuroadaptive changes and behavioral effects after a sensitization regime of MDPV

et al. 2019

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“…In previous studies [34,48] we found that, although repeated exposure to MDPV resulted in an increase in ΔFosB expression, as it occurs after cocaine exposure, other factors were not affected by this cathinone derivative. This suggested that additional pathways are involved in the MDPV effects.…”

Section: Discussionmentioning

confidence: 54%

“…In a previous work, we reported that exposure of adolescent mice to MDPV sensitizes to cocaine effects and induces a higher vulnerability to cocaine abuse in adulthood [48]. Cocaine abuse represents a heavy burden of disease in many countries, becoming a global problem.…”

Section: Discussionmentioning

confidence: 95%

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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

Duart-Castells

López-Arnau

Vizcaíno

et al. 2019

Biochemical Pharmacology

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“…The SA experiment was carried out in mouse operant chambers (Model ENV‐307A‐CT, Med Associates, Inc. Cibertec S.A.), as previously described with some minor modifications (López‐Arnau et al, ; Luján et al, ; Soria, Barbano, Maldonado, & Valverde, ). The chambers were housed in sound‐ and light‐attenuated boxes and contained two holes, one of which was defined as active and the other as inactive.…”

Section: Methodsmentioning

confidence: 99%

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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Background and Purpose Alcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring. Experimental Approach Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement. Key Results The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement. Conclusion and Implications Our findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.

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Exposure of adolescent mice to 3,4‐methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood

Abstract: MDPV exposure during adolescence induced long-lasting adaptive changes related to enhanced responsiveness to cocaine in the adult mice that seems to lead to a higher vulnerability to cocaine abuse. This particular behaviour correlated with increased expression of ΔFosB.

Cited by 21 publications

References 56 publications

Neuroadaptive changes and behavioral effects after a sensitization regime of MDPV

Neuroadaptive changes and behavioral effects after a sensitization regime of MDPV

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

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

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