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Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure.
Neurotox Res. 2019 Jul; 36(1):132-143.NR

Abstract

Designer drug mixtures popularized as "bath salts" often contain the synthetic cathinones 3,4 methylenedioxypyrovalerone (MDPV), mephedrone, and methylone in various combinations. However, most preclinical investigations have only assessed the effects of individual bath salt constituents, and little is known about whether co-exposure to MDPV, mephedrone, and methylone produces significant neuropharmacological interactions. This study evaluated and compared how MDPV, mephedrone, and methylone influence discrete brain tissue dopamine (DA) levels and motor stimulant responses in mice when administered alone and as a ternary mixture. Male adolescent Swiss-Webster mice received intraperitoneal injections of saline or 1 or 10 mg/kg doses of MDPV, mephedrone, or methylone, or a cocktail of all three cathinones at doses of 1, 3.3, or 10 mg/kg each. The effect of each treatment on DA and DA metabolite levels in mesolimbic and nigrostriatal brain tissue was quantified 15 min after a single exposure using HPLC-ECD. Additionally, locomotor activity was recorded in mice after acute (day 1) and chronic intermittent (day 7) dosing. MDPV, mephedrone, and methylone produced dose-related increases in mesolimbic and nigrostriatal DA levels that were significantly enhanced following their co-administration. In addition, mice treated with the cathinone cocktail displayed decreased locomotor activity on day 1 that was exacerbated by day 7 and not observed with any of the drugs alone. Our findings demonstrate a significant enhanced effect of MDPV, mephedrone, and methylone on both DA, and these effects on DA result in significant alterations in locomotor activity.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN, USA.Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN, USA.Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN, USA.Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Box 70594, Johnson City, TN, USA. pond@etsu.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30879275

Citation

Allen, Serena A., et al. "Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure." Neurotoxicity Research, vol. 36, no. 1, 2019, pp. 132-143.
Allen SA, Tran LH, Oakes HV, et al. Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure. Neurotox Res. 2019;36(1):132-143.
Allen, S. A., Tran, L. H., Oakes, H. V., Brown, R. W., & Pond, B. B. (2019). Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure. Neurotoxicity Research, 36(1), 132-143. https://doi.org/10.1007/s12640-019-00020-2
Allen SA, et al. Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure. Neurotox Res. 2019;36(1):132-143. PubMed PMID: 30879275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopaminergic Effects of Major Bath Salt Constituents 3,4-Methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone Are Enhanced Following Co-exposure. AU - Allen,Serena A, AU - Tran,Lily H, AU - Oakes,Hannah V, AU - Brown,Russell W, AU - Pond,Brooks B, Y1 - 2019/03/16/ PY - 2018/09/26/received PY - 2019/02/27/accepted PY - 2019/02/13/revised PY - 2019/3/18/pubmed PY - 2020/1/10/medline PY - 2019/3/18/entrez KW - Bath salts KW - Locomotor activity KW - Mephedrone KW - Methylenedioxypyrovalerone KW - Methylone KW - Synthetic cathinones SP - 132 EP - 143 JF - Neurotoxicity research JO - Neurotox Res VL - 36 IS - 1 N2 - Designer drug mixtures popularized as "bath salts" often contain the synthetic cathinones 3,4 methylenedioxypyrovalerone (MDPV), mephedrone, and methylone in various combinations. However, most preclinical investigations have only assessed the effects of individual bath salt constituents, and little is known about whether co-exposure to MDPV, mephedrone, and methylone produces significant neuropharmacological interactions. This study evaluated and compared how MDPV, mephedrone, and methylone influence discrete brain tissue dopamine (DA) levels and motor stimulant responses in mice when administered alone and as a ternary mixture. Male adolescent Swiss-Webster mice received intraperitoneal injections of saline or 1 or 10 mg/kg doses of MDPV, mephedrone, or methylone, or a cocktail of all three cathinones at doses of 1, 3.3, or 10 mg/kg each. The effect of each treatment on DA and DA metabolite levels in mesolimbic and nigrostriatal brain tissue was quantified 15 min after a single exposure using HPLC-ECD. Additionally, locomotor activity was recorded in mice after acute (day 1) and chronic intermittent (day 7) dosing. MDPV, mephedrone, and methylone produced dose-related increases in mesolimbic and nigrostriatal DA levels that were significantly enhanced following their co-administration. In addition, mice treated with the cathinone cocktail displayed decreased locomotor activity on day 1 that was exacerbated by day 7 and not observed with any of the drugs alone. Our findings demonstrate a significant enhanced effect of MDPV, mephedrone, and methylone on both DA, and these effects on DA result in significant alterations in locomotor activity. SN - 1476-3524 UR - https://www.unboundmedicine.com/medline/citation/30879275/Dopaminergic_Effects_of_Major_Bath_Salt_Constituents_3,4-Methylenedioxypyrovalerone_(MDPV),_Mephedrone,_and_Methylone_Are_Enhanced_Following_Co-exposure L2 - https://dx.doi.org/10.1007/s12640-019-00020-2 DB - PRIME DP - Unbound Medicine ER -