title: Reinforcing and neurochemical effects of the "bath salts" constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats.
abstract: 3,4-Methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) are synthetic drugs found in so-called "bath salts" products. Both drugs exert their effects by interacting with monoamine transporter proteins. MDPV is a potent uptake blocker at transporters for dopamine and norepinephrine while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT).
  
  
  
  We hypothesized that prominent 5-HT-releasing actions of methylone would render this drug less reinforcing than MDPV.
  
  
  
  To test this hypothesis, we compared behavioral effects of MDPV and methylone using intravenous (i.v.) self-administration on a fixed-ratio 1 schedule in male rats. Additionally, neurochemical effects of the drugs were examined using in vivo microdialysis in nucleus accumbens, in a separate cohort of rats.
  
  
  
  MDPV self-administration (0.03 mg/kg/inj) was acquired rapidly and reached 40 infusions per session, similar to the effects of cocaine (0.5 mg/kg/inj), by the end of training. In contrast, methylone self-administration (0.3 and 0.5 mg/kg/inj) was acquired slowly, and response rates only reached 20 infusions per session by the end of training. In dose substitution studies, MDPV and cocaine displayed typical inverted U-shaped dose-effect functions, but methylone did not. In vivo microdialysis revealed that i.v. MDPV (0.1 and 0.3 mg/kg) increased extracellular dopamine while i.v. methylone (1 and 3 mg/kg) increased extracellular dopamine and 5-HT.
  
  
  
  Our findings support the hypothesis that elevations in extracellular 5-HT in the brain can dampen positive reinforcing effects of cathinone-type drugs. Nevertheless, MDPV and methylone are both self-administered by rats, suggesting these drugs possess significant abuse liability in humans.
authors: Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA. cschind@helix.nih.gov.
authors: Charles W
authors: CW
authors: Schindler
authors: Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
authors: Eric B
authors: EB
authors: Thorndike
authors: Preclinical Pharmacology Section, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
authors: Steven R
authors: SR
authors: Goldberg
authors: Designer Drug Research Unit, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
authors: Kurt R
authors: KR
authors: Lehner
authors: Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53706, USA.
authors: Nicholas V
authors: NV
authors: Cozzi
authors: School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors: Simon D
authors: SD
authors: Brandt
authors: Designer Drug Research Unit, Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA.
authors: Michael H
authors: MH
authors: Baumann
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D011759:Pyrrolidines; D008694:Methamphetamine; D003042:Cocaine; C400939:methylone; D004298:Dopamine; D000094982:Synthetic Cathinone
keywords: 3,4-Methylenedioxypyrovalerone (MDPV); Cocaine; Methylone; Microdialysis; Rats; Self-administration