Effects of Environmental Variables on the Pharmacological Actions of “Bath Salts” Constituent 3,4‐Methylenedioxypyrovalerone (MDPV) in Mice

Abstract

Synthetic analogues of cathinone are the active constituents of abused “bath salts” products. 3,4‐methylenedioxypyrovalerone (MDPV) is among the most well‐studied synthetic cathinone given its prevalence in these abused commercial preparations, and it is increasingly used by humans in crowded, hot, and sensory‐rich environments. Given the structural similarity of MDPV to 3,4‐methylenedioxymethamphetamine (MDMA) – the effects of which are dramatically impacted by crowding and ambient temperature — it was of interest to investigate the modulatory effects of similar environmental variables on MDPV‐elicited toxicity and locomotor stimulant effects in mice. Ambient temperature experiments were performed in sound‐attenuating temperature‐controlled enclosures equipped with biotelemetry receivers for recording of horizontal locomotor activity within the home cage. Groups of singly housed mice implanted with radiotelemetry probes were water deprived for 21 hrs, then given a 3‐hr period to orally self‐administer 0.3 mg/ml MDPV or 0.1% quinine solution for 10 consecutive days while the ambient temperature was maintained at 20° or 28°C. Body weight, drug intake, and locomotor activity were measured across successive sessions. Intake of MDPV escalated across successive sessions, such that the dose of self‐administered MDPV was significantly higher on the last 3 days than observed on the first day. In contrast, consumption of quinine did not escalate. There was initially no effect of ambient temperature on quinine or MDPV consumption, but MDPV consumption escalated more rapidly at the 28°C condition. Consumption of MDPV solutions stimulated locomotor activity above levels observed following quinine drinking in both ambient temperature conditions. Body weights remained relatively unchanged. In separate studies, mice were housed singly or in groups of 3 or 6, then administered saline or 0.3, 1.0, 3.0, 10.0, or 17.8 mg/kg MDPV via intraperitoneal injections every 2 hours for a total of 4 injections. Rectal temperatures were obtained before each injection and 2 hours after the 4th injection. Brain regions were collected for neurochemical analysis 10 days after the last MDPV injection. There was no difference in rectal temperature between the crowding conditions prior to MDPV administration, and administration of MDPV did not alter rectal temperature in any housing condition. Body weights decreased as the MDPV dose and crowding condition increased. These experiments suggest that, similar to structurally‐related psychostimulants like MDMA, the pharmacological actions of MDPV are also impacted by environmental variables associated with the settings in which the drug is commonly abused in humans.Support or Funding InformationThese studies supported by DA039195, DA022981 and the UAMS Center for Translational Neuroscience.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.