Effects of Ambient Temperature and Social Housing on Locomotor Activity, Thermoregulation, and Weight Loss Following “Binge” Administration of Structurally‐Related Abused Psychostimulants

Abstract

3,4‐methylenedioxypyrovalerone (MDPV) and α‐pyrrolidinopentiophenone (α‐PVP) are common active constituents of abused “bath salts” products. The structures of these synthetic cathinone analogues differ only in that MDPV contains a methylenedioxy ring. Additionally, MDPV is structurally similar to the amphetamine analogue 3,4‐methylenedioxymethamphetamine (MDMA), which differs fromthe structure of methamphetamine (METH) only by the addition of a methylenedioxy ring. MDPV, α‐PVP, MDMA, and METH are four psychostimulants often used interchangeably by humans in crowded, hot environments. The effects of MDMA are known to be dramatically impacted by crowding and ambient temperature and because of the structural similarities and use patterns in humans, it was of interest to investigate the modulatory effects of such environmental variables on the in vivo pharmacology of the four compounds in mice. In the present studies, adult male NIH Swiss mice were housed singly or in groups of 3 or 6, at 20°C, then administered a “binge” regimen of 1.0, 3.0, or 10.0 mg/kg MDPV, α‐PVP, MDMA or METH, or repeated saline, via intraperitoneal injection, every 2 hours for a total of 4 injections. Locomotor activity and core temperature were continuously collected throughout drug administration, continuing 2 hours after the 4th injection. The lowest dose per social housing condition different from saline was repeated at an elevated temperature of 28°C. Doses were limited by lethal effects which were potentiated both by the increased ambient temperature and social housing conditions. Increased ambient temperature resulted in increased locomotor activity for all compounds, and an increased hyperthermic effect occurred in animals administered MDPV or MDMA, both methylenedioxy ring containing compounds. No pronounced differences regarding body weight and core temperature as a function of social housing were observed. Brain regions (including hippocampus and striatum) were collected for neurochemical analysis 10 days after the last injection. Regions from one hemisphere will be processed and analyzed for tissue content of monoamines and their primary metabolites by HPLC, while samples from the other hemisphere will be utilized to determine GLUT2 concentration via western blotting. These studies suggest that the addition of specific moieties, in this case a methylenedioxy ring, to structurally similiar cathinones and amphetamines can result in same effect compared to the parent compound.Support or Funding InformationThese studies supported by DA039195, DA022981 and the UAMS Center for Translational Neuroscience.