Abstract
3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit “bath salts” products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(−)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(−)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(−)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(−)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(−)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse.
Footnotes
- Received September 21, 2015.
- Accepted December 30, 2015.
This research was supported by the University of Arkansas for Medical Sciences Center for Translational Neuroscience [Grant RR020146], the University of Arkansas for Medical Sciences Translational Research Institute [Grant RR029884], and the National Institutes of Health National Institute on Drug Abuse [Grant T32DA022981]. A portion of this work was supported by the National Institutes of Health Intramural Research Programs of the National Institute on Drug Abuse and the National Institute of Alcohol Abuse and Alcoholism. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse, the National Institute of Alcohol Abuse and Alcoholism, or the National Institutes of Health.
This work was presented, in part, in B.M.G.’s doctoral dissertation defense as follows: Gannon BM (2015) In Vivo Characterization of Major ‘Bath Salt’ Constituent 3,4-Methylenedioxypyrovalerone (MDPV) in Mice. Doctoral dissertation, University of Arkansas for Medical Sciences, Little Rock, AR.
- U.S. Government work not protected by U.S. copyright
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