title: Sensitization to the locomotor stimulant effects of "bath salt" constituents, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), in male Sprague-Dawley rats.
abstract: Synthetic cathinones, 4-methylmethcathinone (4-MMC) and 3,4-methylenedioxypyrovalerone (MDPV), serve as a substrate or blocker at monoaminergic transporters, respectively, and produce locomotor stimulant effects in rodents. The present study investigated in rats the effects of repeated exposure to 4-MMC, MDPV, or mixtures of the two on the induction of locomotor sensitization and expression of cross-sensitization to cocaine.
  
  
  
  Seventy-two male Sprague-Dawley rats received daily intraperitoneal injections of saline, MDPV (0.5mg/kg), 4-MMC (0.5, 1.0, or 2.0mg/kg) or mixtures of 0.5mg/kg MDPV+4-MMC (0.5, 1.0, or 2.0mg/kg) for seven consecutive days. Locomotor activity was recorded on days 1 and 7 and again after an acute injection of 5mg/kg cocaine following a 10day drug washout period.
  
  
  
  Rats injected with 0.5mg/kg MDPV, 0.5, 1.0, or 2.0mg/kg 4-MMC, or 2.0mg/kg 4-MMC+0.5mg/kg MDPV displayed time-dependent increases in horizontal activity that were augmented on day 7 compared to day 1. In addition, rats pretreated with 0.5mg/kg MDPV, 2.0mg/kg 4-MMC, or mixtures of 4-MMC+MDPV displayed an enhanced response to cocaine.
  
  
  
  Locomotor responses sensitize to MDPV and to certain mixtures of MDPV and 4-MMC following repeated dosing. Furthermore, previous exposure to these substances may produce cross-sensitization to the locomotor stimulant effects of cocaine. Considered together with recent findings that 4-MMC and MDPV have different sites of action, but both influence monoaminergic functioning, further investigations utilizing a variety of behavioral assays may prove informative regarding the abuse liability of synthetic cathinone mixtures.
authors.affiliation: Department of Psychology, Western Michigan University, Kalamazoo, MI, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Berquist
authors.affiliation: Department of Psychology, Western Michigan University, Kalamazoo, MI, United States.
authors.forename: Haily K
authors.initials: HK
authors.lastname: Traxler
authors.affiliation: Department of Psychology, Western Michigan University, Kalamazoo, MI, United States.
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Mahler
authors.affiliation: Department of Psychology, Western Michigan University, Kalamazoo, MI, United States. Electronic address: lisa.baker@wmich.edu.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Baker
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000633:toxicity*; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003042:Cocaine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D011759:Pyrrolidines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000094982:Synthetic Cathinone
chemical_list: D052117:Benzodioxoles; D000697:Central Nervous System Stimulants; D011759:Pyrrolidines; D008694:Methamphetamine; C548233:mephedrone; D003042:Cocaine; D000094982:Synthetic Cathinone
keywords: 3,4-; 4-MMC; 4-Methylmethcathinone; Bath salts; Cocaine; Cross-sensitization<; Locomotor sensitization; MDPV; Mephedrone; Methylenedioxypyrovalerone; Rats; Synthetic cathinones