In vivo effects of “bath salt” constituent 3,4‐ methylenedioxypyrovalerone (MDPV) in mice: contribution of ambient temperature and monoamines

Abstract

Designer stimulants are rapidly emerging as drugs of abuse. Marketed as “bath salts” or “plant food,” these commercial products typically contain cathinone analogues such as 3,4‐methylenedioxypyrovalerone (MDPV), but little is known about the underlying in vivo pharmacology of these drugs. In these studies, we assessed the effects of MDPV on core temperature and locomotor activity in mice as a function of ambient temperature. Further studies extended these findings by depleting serotonin (5‐ HT) or catecholamines (DA and NE) in order to gauge the role of these neurotransmitter systems in the in vivo effects of MDPV. Across a range of doses, MDPV elicited locomotor stimulant effects at 20°C, and increasing the ambient temperature to 29°C potentiated this action. Similarly, MDPV induced hyperthermic effects in mice at the cool ambient temperature, but hyperthermia was even more profound at 29°C, where lethality also occurred. Depletion of central 5‐HT did not alter the locomotor stimulant effects of MDPV, but exacerbated the hyperthermic effects of this compound, while depletion of catecholamines attenuated the locomotor stimulant effects of MDPV without altering the thermoregulatory effects of this drug. These findings suggest that ambient temperature is a critical factor in evaluating the in vivo pharmacology of MDPV, which seems to involve a mixture of serotonergic, dopaminergic, and perhaps noradrenergic systems in the mouse. In vivo studies were supported by US PHS Grant RR020146 and a Pilot Research Award from the University of Arkansas for Medical Sciences Center for Clinical and Translational Research (RR029884). The work of the Drug Design and Synthesis Section was supported by the NIH Intramural Research Programs of the NIDA and the NIAAA.