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

BackgroundSynthetic 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. MethodsSeventy-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. ResultsRats 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. ConclusionsLocomotor 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.