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Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats.
Neuropsychopharmacology. 2018 03; 43(4):761-769.N

Abstract

Bath salts use is associated with high rates of abuse, toxicity, and death. Bath salt preparations often contain mixtures of drugs including multiple synthetic cathinones (eg, 3,4-methylenedioxypyrovalerone (MDPV) or 3,4-methylenedioxymethcathinone (methylone)) or synthetic cathinones and caffeine; however, little is known about whether interactions among bath salt constituents contribute to the abuse-related effects of bath salts preparations. This study used male Sprague-Dawley rats responding under a progressive ratio schedule to quantify the reinforcing effectiveness of MDPV, methylone, and caffeine, administered alone and as binary mixtures (n=12 per mixture). Each mixture was evaluated at four ratios (10 : 1, 3 : 1, 1 : 1, and 1 : 3) relative to the mean ED50 for each drug alone. Dose-addition analyses were used to determine the predicted, additive effect for each dose pair within each drug mixture. MDPV, methylone, and caffeine maintained responding in a dose-dependent manner, with MDPV being the most potent and effective, and caffeine being the least potent and effective of the three bath salts constituents. High levels of responding were also maintained by each of the bath salts mixtures. Although the nature of the interactions tended toward additivity for most bath salts mixtures, supra-additive (3 : 1 MDPV : caffeine, and 3 : 1 and 1 : 1 methylone : caffeine) and sub-additive (3 : 1, 1 : 1, and 1 : 3 MDPV : methylone) interactions were also observed. Together, these findings demonstrate that the composition of bath salts preparations can have an impact on both their reinforcing potency and effectiveness, and suggest that such interactions among constituent drugs could contribute to the patterns of use and effects reported by human bath salts users.

Authors+Show Affiliations

Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.Molecular Targets and Medications Discovery Branch, NIDA and NIAAA, Bethesda, MD, USA.Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. South Texas Veterans Health Care System, San Antonio, TX, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28677665

Citation

Gannon, Brenda M., et al. "Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies With 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 43, no. 4, 2018, pp. 761-769.
Gannon BM, Galindo KI, Mesmin MP, et al. Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats. Neuropsychopharmacology. 2018;43(4):761-769.
Gannon, B. M., Galindo, K. I., Mesmin, M. P., Rice, K. C., & Collins, G. T. (2018). Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 43(4), 761-769. https://doi.org/10.1038/npp.2017.141
Gannon BM, et al. Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies With 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats. Neuropsychopharmacology. 2018;43(4):761-769. PubMed PMID: 28677665.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reinforcing Effects of Binary Mixtures of Common Bath Salt Constituents: Studies with 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-Methylenedioxymethcathinone (methylone), and Caffeine in Rats. AU - Gannon,Brenda M, AU - Galindo,Kayla I, AU - Mesmin,Melson P, AU - Rice,Kenner C, AU - Collins,Gregory T, Y1 - 2017/07/05/ PY - 2017/03/13/received PY - 2017/06/26/revised PY - 2017/06/29/accepted PY - 2017/7/6/pubmed PY - 2019/3/12/medline PY - 2017/7/6/entrez SP - 761 EP - 769 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 43 IS - 4 N2 - Bath salts use is associated with high rates of abuse, toxicity, and death. Bath salt preparations often contain mixtures of drugs including multiple synthetic cathinones (eg, 3,4-methylenedioxypyrovalerone (MDPV) or 3,4-methylenedioxymethcathinone (methylone)) or synthetic cathinones and caffeine; however, little is known about whether interactions among bath salt constituents contribute to the abuse-related effects of bath salts preparations. This study used male Sprague-Dawley rats responding under a progressive ratio schedule to quantify the reinforcing effectiveness of MDPV, methylone, and caffeine, administered alone and as binary mixtures (n=12 per mixture). Each mixture was evaluated at four ratios (10 : 1, 3 : 1, 1 : 1, and 1 : 3) relative to the mean ED50 for each drug alone. Dose-addition analyses were used to determine the predicted, additive effect for each dose pair within each drug mixture. MDPV, methylone, and caffeine maintained responding in a dose-dependent manner, with MDPV being the most potent and effective, and caffeine being the least potent and effective of the three bath salts constituents. High levels of responding were also maintained by each of the bath salts mixtures. Although the nature of the interactions tended toward additivity for most bath salts mixtures, supra-additive (3 : 1 MDPV : caffeine, and 3 : 1 and 1 : 1 methylone : caffeine) and sub-additive (3 : 1, 1 : 1, and 1 : 3 MDPV : methylone) interactions were also observed. Together, these findings demonstrate that the composition of bath salts preparations can have an impact on both their reinforcing potency and effectiveness, and suggest that such interactions among constituent drugs could contribute to the patterns of use and effects reported by human bath salts users. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/28677665/Reinforcing_Effects_of_Binary_Mixtures_of_Common_Bath_Salt_Constituents:_Studies_with_3,4-Methylenedioxypyrovalerone_(MDPV),_3,4-Methylenedioxymethcathinone_(methylone),_and_Caffeine_in_Rats L2 - http://dx.doi.org/10.1038/npp.2017.141 DB - PRIME DP - Unbound Medicine ER -