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Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships
Rationale The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated. Objective and methods To stud...
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| Published in: | Psychopharmacology 2019-03, Vol.236 (3), p.891-901 |
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| container_title | Psychopharmacology |
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| creator | Benturquia, Nadia Chevillard, Lucie Poiré, Christophe Roussel, Olivier Cohier, Camille Declèves, Xavier Laplanche, Jean-Louis Etheve-Quelquejeu, Mélanie Chen, Huixiong Mégarbane, Bruno |
| description | Rationale
The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated.
Objective and methods
To study 3,4-methylenedioxypyrovalerone (MDPV; 3 mg/kg) and mephedrone (4-MMC; 30 mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal
E
max
modeling.
Results
Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (
p
|
| doi_str_mv | 10.1007/s00213-018-4962-0 |
| format | article |
| fullrecord | <record><control><sourceid>gale_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_01899917v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A590346176</galeid><sourcerecordid>A590346176</sourcerecordid><originalsourceid>FETCH-LOGICAL-c473t-aa0c3a68bba9004a0fea4129023ea767382d861f8eee1aea294ae3c71c7d11323</originalsourceid><addsrcrecordid>eNp1kstu1DAUhiMEokPhAdggS2xAIh3fJpdVNaoKrTQSG1hbjnMycZXYwU4G5q14xJ40vQgEySKW_f1__J9zkuQto2eM0nwdKeVMpJQVqSwzntJnyYpJwVNOc_48WVEqRCrYpjhJXsV4Q_GRhXyZnPCyzJnM2Cr5fR3J2AIRn2Taw9geO3C19b-OwzH4g-4geAfrHoYW6nlJjO8r6_RovSMB4uBdtFUHpPGBgGu1M1CTONp-6rQbCTQNmDGeky0JesSDqT6Sn3ZsiXUHQG6_WPnm7hoLvjYebdwYHn7T3S1ia4f4OnnR6C7Cm_vvafL98-W3i6t09_XL9cV2lxqZizHVmhqhs6KqdImpNW1AS8ZLygXoPMtFwesiY00BAEyD5qXUIEzOTF4zJrg4TT4uvq3u1BBsr8NReW3V1Xan5j2selmWLD8wZD8s7BD8jwlTqd5GAx1WAPwUFaeZ5BIFGaLv_0Jv_BQcJpkpscHObfgTtccOKOsaj7Uws6nabkoqsHX57HX2DwrfGnqLJYTG4v4fArYITPAxBmgegzGq5olSy0TN2dQ8UYqi5t39haeqh_pR8TBCCPAFiHjk9hCeEv3f9RZMq9g4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2063520752</pqid></control><display><type>article</type><title>Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships</title><source>EBSCOhost SPORTDiscus with Full Text</source><source>Springer Link</source><creator>Benturquia, Nadia ; Chevillard, Lucie ; Poiré, Christophe ; Roussel, Olivier ; Cohier, Camille ; Declèves, Xavier ; Laplanche, Jean-Louis ; Etheve-Quelquejeu, Mélanie ; Chen, Huixiong ; Mégarbane, Bruno</creator><creatorcontrib>Benturquia, Nadia ; Chevillard, Lucie ; Poiré, Christophe ; Roussel, Olivier ; Cohier, Camille ; Declèves, Xavier ; Laplanche, Jean-Louis ; Etheve-Quelquejeu, Mélanie ; Chen, Huixiong ; Mégarbane, Bruno</creatorcontrib><description><![CDATA[Rationale
The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated.
Objective and methods
To study 3,4-methylenedioxypyrovalerone (MDPV; 3 mg/kg) and mephedrone (4-MMC; 30 mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal
E
max
modeling.
Results
Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (
p
< 0.001) and 4-MMC (
p
< 0.01) alone. The pharmacokinetic profile of MDPV, but not 4-MMC, was significantly modified with the combination resulting in decreases in
C
max
(16.4 ± 5.5 versus 62.2 ± 14.2 μg/L,
p
< 0.05) and AUC
0 → ∞
(708 ± 91 versus 3316 ± 682 μg/L/min,
p
< 0.01) and increases in V/F (582.6 ± 136.8 versus 115.9 ± 42.7 L/kg,
p
< 0.05) and Cl/F (4.6 ± 0.7 versus 1.2 ± 0.4 L/kg/min,
p
< 0.01) in comparison to MDPV alone. The sigmoidal
E
max
model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC
50
, 0.043 versus 0.7 μmol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3.
Conclusion
An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.]]></description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-018-4962-0</identifier><identifier>PMID: 29971461</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Bioavailability ; Biomedical and Life Sciences ; Biomedicine ; Dopamine receptors ; Drug testing ; Life Sciences ; Locomotor activity ; Neurons and Cognition ; Neurosciences ; Original Investigation ; Pharmaceutical sciences ; Pharmacokinetics ; Pharmacology ; Pharmacology/Toxicology ; Psychiatry ; Psychology and behavior ; Resveratrol ; Rodents</subject><ispartof>Psychopharmacology, 2019-03, Vol.236 (3), p.891-901</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Psychopharmacology is a copyright of Springer, (2018). All Rights Reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-aa0c3a68bba9004a0fea4129023ea767382d861f8eee1aea294ae3c71c7d11323</citedby><cites>FETCH-LOGICAL-c473t-aa0c3a68bba9004a0fea4129023ea767382d861f8eee1aea294ae3c71c7d11323</cites><orcidid>0000-0002-2522-2764 ; 0000-0002-4105-3243 ; 0000-0003-2910-9117 ; 0000-0002-9778-7158</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29971461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://u-paris.hal.science/hal-01899917$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Benturquia, Nadia</creatorcontrib><creatorcontrib>Chevillard, Lucie</creatorcontrib><creatorcontrib>Poiré, Christophe</creatorcontrib><creatorcontrib>Roussel, Olivier</creatorcontrib><creatorcontrib>Cohier, Camille</creatorcontrib><creatorcontrib>Declèves, Xavier</creatorcontrib><creatorcontrib>Laplanche, Jean-Louis</creatorcontrib><creatorcontrib>Etheve-Quelquejeu, Mélanie</creatorcontrib><creatorcontrib>Chen, Huixiong</creatorcontrib><creatorcontrib>Mégarbane, Bruno</creatorcontrib><title>Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description><![CDATA[Rationale
The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated.
Objective and methods
To study 3,4-methylenedioxypyrovalerone (MDPV; 3 mg/kg) and mephedrone (4-MMC; 30 mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal
E
max
modeling.
Results
Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (
p
< 0.001) and 4-MMC (
p
< 0.01) alone. The pharmacokinetic profile of MDPV, but not 4-MMC, was significantly modified with the combination resulting in decreases in
C
max
(16.4 ± 5.5 versus 62.2 ± 14.2 μg/L,
p
< 0.05) and AUC
0 → ∞
(708 ± 91 versus 3316 ± 682 μg/L/min,
p
< 0.01) and increases in V/F (582.6 ± 136.8 versus 115.9 ± 42.7 L/kg,
p
< 0.05) and Cl/F (4.6 ± 0.7 versus 1.2 ± 0.4 L/kg/min,
p
< 0.01) in comparison to MDPV alone. The sigmoidal
E
max
model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC
50
, 0.043 versus 0.7 μmol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3.
Conclusion
An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.]]></description><subject>Bioavailability</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Dopamine receptors</subject><subject>Drug testing</subject><subject>Life Sciences</subject><subject>Locomotor activity</subject><subject>Neurons and Cognition</subject><subject>Neurosciences</subject><subject>Original Investigation</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacokinetics</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Psychiatry</subject><subject>Psychology and behavior</subject><subject>Resveratrol</subject><subject>Rodents</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kstu1DAUhiMEokPhAdggS2xAIh3fJpdVNaoKrTQSG1hbjnMycZXYwU4G5q14xJ40vQgEySKW_f1__J9zkuQto2eM0nwdKeVMpJQVqSwzntJnyYpJwVNOc_48WVEqRCrYpjhJXsV4Q_GRhXyZnPCyzJnM2Cr5fR3J2AIRn2Taw9geO3C19b-OwzH4g-4geAfrHoYW6nlJjO8r6_RovSMB4uBdtFUHpPGBgGu1M1CTONp-6rQbCTQNmDGeky0JesSDqT6Sn3ZsiXUHQG6_WPnm7hoLvjYebdwYHn7T3S1ia4f4OnnR6C7Cm_vvafL98-W3i6t09_XL9cV2lxqZizHVmhqhs6KqdImpNW1AS8ZLygXoPMtFwesiY00BAEyD5qXUIEzOTF4zJrg4TT4uvq3u1BBsr8NReW3V1Xan5j2selmWLD8wZD8s7BD8jwlTqd5GAx1WAPwUFaeZ5BIFGaLv_0Jv_BQcJpkpscHObfgTtccOKOsaj7Uws6nabkoqsHX57HX2DwrfGnqLJYTG4v4fArYITPAxBmgegzGq5olSy0TN2dQ8UYqi5t39haeqh_pR8TBCCPAFiHjk9hCeEv3f9RZMq9g4</recordid><startdate>20190301</startdate><enddate>20190301</enddate><creator>Benturquia, Nadia</creator><creator>Chevillard, Lucie</creator><creator>Poiré, Christophe</creator><creator>Roussel, Olivier</creator><creator>Cohier, Camille</creator><creator>Declèves, Xavier</creator><creator>Laplanche, Jean-Louis</creator><creator>Etheve-Quelquejeu, Mélanie</creator><creator>Chen, Huixiong</creator><creator>Mégarbane, Bruno</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-2522-2764</orcidid><orcidid>https://orcid.org/0000-0002-4105-3243</orcidid><orcidid>https://orcid.org/0000-0003-2910-9117</orcidid><orcidid>https://orcid.org/0000-0002-9778-7158</orcidid></search><sort><creationdate>20190301</creationdate><title>Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships</title><author>Benturquia, Nadia ; Chevillard, Lucie ; Poiré, Christophe ; Roussel, Olivier ; Cohier, Camille ; Declèves, Xavier ; Laplanche, Jean-Louis ; Etheve-Quelquejeu, Mélanie ; Chen, Huixiong ; Mégarbane, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-aa0c3a68bba9004a0fea4129023ea767382d861f8eee1aea294ae3c71c7d11323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Bioavailability</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Dopamine receptors</topic><topic>Drug testing</topic><topic>Life Sciences</topic><topic>Locomotor activity</topic><topic>Neurons and Cognition</topic><topic>Neurosciences</topic><topic>Original Investigation</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacokinetics</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Psychiatry</topic><topic>Psychology and behavior</topic><topic>Resveratrol</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Benturquia, Nadia</creatorcontrib><creatorcontrib>Chevillard, Lucie</creatorcontrib><creatorcontrib>Poiré, Christophe</creatorcontrib><creatorcontrib>Roussel, Olivier</creatorcontrib><creatorcontrib>Cohier, Camille</creatorcontrib><creatorcontrib>Declèves, Xavier</creatorcontrib><creatorcontrib>Laplanche, Jean-Louis</creatorcontrib><creatorcontrib>Etheve-Quelquejeu, Mélanie</creatorcontrib><creatorcontrib>Chen, Huixiong</creatorcontrib><creatorcontrib>Mégarbane, Bruno</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Proquest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Psychology Database (ProQuest)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Benturquia, Nadia</au><au>Chevillard, Lucie</au><au>Poiré, Christophe</au><au>Roussel, Olivier</au><au>Cohier, Camille</au><au>Declèves, Xavier</au><au>Laplanche, Jean-Louis</au><au>Etheve-Quelquejeu, Mélanie</au><au>Chen, Huixiong</au><au>Mégarbane, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2019-03-01</date><risdate>2019</risdate><volume>236</volume><issue>3</issue><spage>891</spage><epage>901</epage><pages>891-901</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><abstract><![CDATA[Rationale
The use of synthetic cathinones as recreational drugs frequently sold in combination has been increasing exponentially. However, the consequences of combining cathinones on the resulting stimulant effects and the pharmacokinetics have been poorly investigated.
Objective and methods
To study 3,4-methylenedioxypyrovalerone (MDPV; 3 mg/kg) and mephedrone (4-MMC; 30 mg/kg)-induced effects on rat locomotor activity and pharmacokinetics, administered alone or in combination by the intragastric route. The pharmacokinetic parameters were determined using non-compartmental analysis and the relationships between the locomotor activity and drug concentrations using sigmoidal
E
max
modeling.
Results
Locomotor activity significantly increased during the first hour post-administration with the MDPV/4-MMC combination in comparison to MDPV (
p
< 0.001) and 4-MMC (
p
< 0.01) alone. The pharmacokinetic profile of MDPV, but not 4-MMC, was significantly modified with the combination resulting in decreases in
C
max
(16.4 ± 5.5 versus 62.2 ± 14.2 μg/L,
p
< 0.05) and AUC
0 → ∞
(708 ± 91 versus 3316 ± 682 μg/L/min,
p
< 0.01) and increases in V/F (582.6 ± 136.8 versus 115.9 ± 42.7 L/kg,
p
< 0.05) and Cl/F (4.6 ± 0.7 versus 1.2 ± 0.4 L/kg/min,
p
< 0.01) in comparison to MDPV alone. The sigmoidal
E
max
model fitted the observed data well; MDPV being markedly more potent than 4-MMC (EC
50
, 0.043 versus 0.7 μmol/L). The enhancing factor representing the MDPV contribution to the alteration in the relationships between locomotor activity and 4-MMC concentrations was 0.3.
Conclusion
An MDPV/4-MMC combination results in enhanced stimulant effects in the rat, despite significant reduction in MDPV bioavailability. Enhanced effects could be explained by increased MDPV distribution and/or possible complementation at the brain dopaminergic targets. However, the exact consequences of the MDPV/4-MMC combination in humans remain to be clarified.]]></abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>29971461</pmid><doi>10.1007/s00213-018-4962-0</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2522-2764</orcidid><orcidid>https://orcid.org/0000-0002-4105-3243</orcidid><orcidid>https://orcid.org/0000-0003-2910-9117</orcidid><orcidid>https://orcid.org/0000-0002-9778-7158</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0033-3158 |
| ispartof | Psychopharmacology, 2019-03, Vol.236 (3), p.891-901 |
| issn | 0033-3158 1432-2072 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01899917v1 |
| source | EBSCOhost SPORTDiscus with Full Text; Springer Link |
| subjects | Bioavailability Biomedical and Life Sciences Biomedicine Dopamine receptors Drug testing Life Sciences Locomotor activity Neurons and Cognition Neurosciences Original Investigation Pharmaceutical sciences Pharmacokinetics Pharmacology Pharmacology/Toxicology Psychiatry Psychology and behavior Resveratrol Rodents |
| title | Is the 3,4-methylendioxypyrovalerone/mephedrone combination responsible for enhanced stimulant effects? A rat study with investigation of the effect/concentration relationships |
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