Conditioned place preference with low dose mixtures of α-pyrrolidinopentiophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV) in male and female Sprague-Dawley rats

Two common constituents of psychoactive “bath salts”, 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinoipentiophenone (α-PVP) belong to a novel class of synthetic chemicals structurally related to the psychostimulant drug, cathinone. Recreational use of MDPV and α-PVP pose serious health risks, which may be exacerbated by concomitant use of both substances. Preclinical psychopharmacology studies have established that MDPV and α-PVP have high abuse liabilities, comparable to that of cocaine and methamphetamine. Whereas polysubstance use is common among recreational users of synthetic cathinones, preclinical behavioral assays can serve to inform potential behavioral health risks of drug mixtures. This study employed a rodent model of conditioned drug reward, conditioned place preference (CPP), to determine if concurrent treatment with MDPV (1 mg/kg) and α-PVP (1 mg/kg) produced stronger locomotor activation or CPP compared to each individual substance. A secondary aim of this study was to assess sex as variable in the behavioral effects of these substances. Females exhibited a stronger response than males to the locomotor stimulant effects of α-PVP and the α-PVP + MDPV mixture. Additionally, the α-PVP + MDPV mixture produced significantly greater increases in activity compared to either drug alone in females. MDPV and the α-PVP + MDPV mixture established CPP in both sexes, whereas α-PVP alone failed to produce CPP in either sex. These results are consistent with previous preclinical study findings that females may be more susceptible to the psychostimulant effects of these synthetic cathinones. Further investigation is warranted to determine the mechanisms responsible for sex differences in the behavioral effects of these drugs.