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

BACKGROUND AND PURPOSE 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits the dopamine transporter (DAT) and is 10-50-fold more potent as a DAT blocker than cocaine, suggesting a high abuse liability. The main objective of th...

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Authors: López Arnau, Raúl, Luján, Miguel Á., Duart Castells, Leticia, Pubill Sánchez, David, Camarasa García, Jordi, Valverde, Olga, Escubedo Rafa, Elena
Format: article
Status:Versión aceptada para publicación
Publication Date:2017
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/167464
Online Access:https://hdl.handle.net/2445/167464
Access Level:Open access
Keyword:Cocaïna
Farmacologia
Antidepressius
Drogues
Adolescència
Ratolins (Animals de laboratori)
Cocaine
Pharmacology
Antidepressants
Drugs of abuse
Adolescence
Mice (Laboratory animals)
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oai_identifier_str oai:recercat.cat:2445/167464
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repository_id_str
spelling Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthoodLópez Arnau, RaúlLuján, Miguel Á.Duart Castells, LeticiaPubill Sánchez, DavidCamarasa García, JordiValverde, OlgaEscubedo Rafa, ElenaCocaïnaFarmacologiaAntidepressiusDroguesAdolescènciaRatolins (Animals de laboratori)CocainePharmacologyAntidepressantsDrugs of abuseAdolescenceMice (Laboratory animals)BACKGROUND AND PURPOSE 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits the dopamine transporter (DAT) and is 10-50-fold more potent as a DAT blocker than cocaine, suggesting a high abuse liability. The main objective of the present study was to assess the consequences of an early (adolescence) MDPV exposure on the psychostimulant, rewarding and reinforcing effects induced by cocaine in adult mice. EXPERIMENTAL APPROACH Twenty-one days after MDPV pretreatment (1.5 mg/kg, s.c., twice daily for 7 days), adult mice were tested with cocaine, using locomotor activity, conditioned place preference and self-administration (SA) paradigms. In parallel, dopamine D2 receptor density and the expression of c-Fos and ΔFosB in the striatum were determined. KEY RESULTS MDPV treatment enhanced the psychostimulant and conditioning effects of cocaine. Acquisition of cocaine SA was unchanged in mice pretreated with MDPV, whereas the breaking point achieved under a progressive ratio programme and reinstatement after extinction were higher in this group of mice. MDPV decreased D2 receptor density but increased ΔFosB expression three-fold. As expected, acute cocaine increased c-Fos expression, but MDPV pretreatment negatively influenced its expression. ΔFosB accumulation declined during MDPV withdrawal, although it remained elevated in adult mice when tested for cocaine effects. CONCLUSION AND IMPLICATIONS 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.Blackwell2020202020172020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion13 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/167464Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1111/bph.13771British Journal of Pharmacology, 2017, vol. 174, num. 10, p. 1161-1173https://doi.org/10.1111/bph.13771info:eu-repo/grantAgreement/EC/H2020/634143(c) The British Pharmacological Society, 2017info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1674642026-05-29T05:05:01Z
dc.title.none.fl_str_mv Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
title Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
spellingShingle Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
López Arnau, Raúl
Cocaïna
Farmacologia
Antidepressius
Drogues
Adolescència
Ratolins (Animals de laboratori)
Cocaine
Pharmacology
Antidepressants
Drugs of abuse
Adolescence
Mice (Laboratory animals)
title_short Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
title_full Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
title_fullStr Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
title_full_unstemmed Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
title_sort Exposure of adolescent mice to 3,4-methylenedioxypyrovalerone increases the psychostimulant, rewarding and reinforcing effects of cocaine in adulthood
dc.creator.none.fl_str_mv López Arnau, Raúl
Luján, Miguel Á.
Duart Castells, Leticia
Pubill Sánchez, David
Camarasa García, Jordi
Valverde, Olga
Escubedo Rafa, Elena
author López Arnau, Raúl
author_facet López Arnau, Raúl
Luján, Miguel Á.
Duart Castells, Leticia
Pubill Sánchez, David
Camarasa García, Jordi
Valverde, Olga
Escubedo Rafa, Elena
author_role author
author2 Luján, Miguel Á.
Duart Castells, Leticia
Pubill Sánchez, David
Camarasa García, Jordi
Valverde, Olga
Escubedo Rafa, Elena
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cocaïna
Farmacologia
Antidepressius
Drogues
Adolescència
Ratolins (Animals de laboratori)
Cocaine
Pharmacology
Antidepressants
Drugs of abuse
Adolescence
Mice (Laboratory animals)
topic Cocaïna
Farmacologia
Antidepressius
Drogues
Adolescència
Ratolins (Animals de laboratori)
Cocaine
Pharmacology
Antidepressants
Drugs of abuse
Adolescence
Mice (Laboratory animals)
description BACKGROUND AND PURPOSE 3,4-Methylenedioxypyrovalerone (MDPV) is a synthetic cathinone with powerful psychostimulant effects. It selectively inhibits the dopamine transporter (DAT) and is 10-50-fold more potent as a DAT blocker than cocaine, suggesting a high abuse liability. The main objective of the present study was to assess the consequences of an early (adolescence) MDPV exposure on the psychostimulant, rewarding and reinforcing effects induced by cocaine in adult mice. EXPERIMENTAL APPROACH Twenty-one days after MDPV pretreatment (1.5 mg/kg, s.c., twice daily for 7 days), adult mice were tested with cocaine, using locomotor activity, conditioned place preference and self-administration (SA) paradigms. In parallel, dopamine D2 receptor density and the expression of c-Fos and ΔFosB in the striatum were determined. KEY RESULTS MDPV treatment enhanced the psychostimulant and conditioning effects of cocaine. Acquisition of cocaine SA was unchanged in mice pretreated with MDPV, whereas the breaking point achieved under a progressive ratio programme and reinstatement after extinction were higher in this group of mice. MDPV decreased D2 receptor density but increased ΔFosB expression three-fold. As expected, acute cocaine increased c-Fos expression, but MDPV pretreatment negatively influenced its expression. ΔFosB accumulation declined during MDPV withdrawal, although it remained elevated in adult mice when tested for cocaine effects. CONCLUSION AND IMPLICATIONS 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.
publishDate 2017
dc.date.none.fl_str_mv 2017
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/167464
url https://hdl.handle.net/2445/167464
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1111/bph.13771
British Journal of Pharmacology, 2017, vol. 174, num. 10, p. 1161-1173
https://doi.org/10.1111/bph.13771
info:eu-repo/grantAgreement/EC/H2020/634143
dc.rights.none.fl_str_mv (c) The British Pharmacological Society, 2017
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) The British Pharmacological Society, 2017
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Blackwell
publisher.none.fl_str_mv Blackwell
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416697879855104
score 15.812429

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