Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat

Luisa Alessandra Atehortua-Martinez, Cyriaque Masniere, Patrizia Campolongo, Stéphanie Chasseigneaux, Jacques Callebert, Clemens Zwergel, Antonello Mai, Jean-Louis Laplanche, Huixiong Chen, Mélanie Etheve-Quelquejeu, Bruno Mégarbane, Nadia Benturquia

Research output: Contribution to journalArticle

Abstract

BACKGROUND:: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability.

AIMS:: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties.

METHODS:: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex.

RESULTS:: Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex.

CONCLUSIONS:: Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.

Original languageEnglish
Pages (from-to)269881118822151
JournalJournal of Psychopharmacology
DOIs
Publication statusE-pub ahead of print - 2018

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Designer Drugs
Baths
Salts
Nucleus Accumbens
Putamen
3,4-methylenedioxypyrovalerone
Locomotion
Prefrontal Cortex
Amphetamines
Dopamine Antagonists

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Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat. / Atehortua-Martinez, Luisa Alessandra; Masniere, Cyriaque; Campolongo, Patrizia; Chasseigneaux, Stéphanie; Callebert, Jacques; Zwergel, Clemens; Mai, Antonello; Laplanche, Jean-Louis; Chen, Huixiong; Etheve-Quelquejeu, Mélanie; Mégarbane, Bruno; Benturquia, Nadia.

In: Journal of Psychopharmacology, 2018, p. 269881118822151.

Research output: Contribution to journalArticle

Atehortua-Martinez, LA, Masniere, C, Campolongo, P, Chasseigneaux, S, Callebert, J, Zwergel, C, Mai, A, Laplanche, J-L, Chen, H, Etheve-Quelquejeu, M, Mégarbane, B & Benturquia, N 2018, 'Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat', Journal of Psychopharmacology, pp. 269881118822151. https://doi.org/10.1177/0269881118822151
Atehortua-Martinez, Luisa Alessandra ; Masniere, Cyriaque ; Campolongo, Patrizia ; Chasseigneaux, Stéphanie ; Callebert, Jacques ; Zwergel, Clemens ; Mai, Antonello ; Laplanche, Jean-Louis ; Chen, Huixiong ; Etheve-Quelquejeu, Mélanie ; Mégarbane, Bruno ; Benturquia, Nadia. / Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat. In: Journal of Psychopharmacology. 2018 ; pp. 269881118822151.
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abstract = "BACKGROUND:: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability.AIMS:: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties.METHODS:: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex.RESULTS:: Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex.CONCLUSIONS:: Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.",
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T1 - Acute and chronic neurobehavioral effects of the designer drug and bath salt constituent 3,4-methylenedioxypyrovalerone in the rat

AU - Atehortua-Martinez, Luisa Alessandra

AU - Masniere, Cyriaque

AU - Campolongo, Patrizia

AU - Chasseigneaux, Stéphanie

AU - Callebert, Jacques

AU - Zwergel, Clemens

AU - Mai, Antonello

AU - Laplanche, Jean-Louis

AU - Chen, Huixiong

AU - Etheve-Quelquejeu, Mélanie

AU - Mégarbane, Bruno

AU - Benturquia, Nadia

PY - 2018

Y1 - 2018

N2 - BACKGROUND:: The substantial increase in use of 3,4-methylenedioxypyrovalerone (MDPV), a popular recreational synthetic cathinone, has raised legitimate questions about its behavioral consequences and abuse liability.AIMS:: The aim of this study was to study MDPV-induced neurobehavioral effects in the rat, using different paradigms traditionally developed to study drug-attributed addictive properties.METHODS:: Different patterns of intraperitoneal 3 mg/kg MDPV administration were investigated. Consequences on rat horizontal locomotion and behavior of acute, intermittent (once daily dosing over 10 days), and binge (three-time daily dosing for 3 days) MDPV administration as well as challenge after 10 day MDPV withdrawal were studied. The dopamine receptor-D1 antagonist, SCH23390, was bilaterally infused in the nucleus accumbens to determine the role of D1-receptors in MDPV-related effects on the associative memory recall using the conditioned place preference paradigm. In addition, in a separate experience using western blot, we investigated the effects of chronic MDPV administration (four injections during 24 h) on ΔFosB expression in the nucleus accumbens, caudate putamen, and prefrontal cortex.RESULTS:: Acute MDPV administration increased stereotypies and open arm entries in the elevated plus maze while SCH23390 abolished MDPV-induced enhancing effects on memory consolidation. Intermittent MDPV administration resulted in sensitization of MDPV-induced locomotor effects and tolerance during the following challenge. With binge MDPV administration, locomotor activity was not altered despite tolerance onset after challenge. SCH23390 abolished MDPV-induced conditioned place preference. Chronic MDPV administration induced ΔFosB accumulation in the nucleus accumbens, caudate putamen, and prefrontal cortex.CONCLUSIONS:: Our findings clearly show that MDPV produces profound behavioral alterations mediated by the activation of the dopaminergic system similarly to other amphetamines.

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DO - 10.1177/0269881118822151

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