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Sex differences in 3,4-methylenedioxypyrovalerone (MDPV)-induced taste avoidance and place preferences.

ABSTRACT: Synthetic cathinones, otherwise known as "bath salts", have gained significant attention in the last few years as a result of increased use and abuse. One such compound, 3,4-methylenedioxypyrovalerone (MDPV), is pharmacologically and behaviorally similar to cocaine and has been shown to possess both aversive and rewarding effects. For a host of other drugs, each of these effects (and their relative balance) can be influenced by a variety of factors, including sex, which in turn impacts drug taking behavior. In this context, the present assessment sought to determine whether males and females differed in MDPV-induced CTA and CPP. Both male and female Sprague-Dawley rats underwent a combined CTA/CPP procedure, in which an injection of one of three doses of MDPV (1.0, 1.8 or 3.2mg/kg) was paired with both a novel saccharin solution and a novel environment and changes in preferences for these stimuli were examined. Taste avoidance was evident in both sexes, although this avoidance was weaker in females compared to males. MDPV also produced place preferences in all drug-treated animals, but these preferences did not vary as a function of sex. The fact that females showed a weaker avoidance response compared to males (despite comparable preferences) suggests that females may have a heightened susceptibility to use and abuse of MDPV, paralleling results seen with cocaine and other stimulants. The present findings extend the behavioral characterization of MDPV and the factors that may alter its aversive and rewarding effects.

SUBMITTER: King HE

PROVIDER: S-EPMC5548123 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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3,4-Methylenedioxypyrovalerone (MDPV)-induced conditioned taste avoidance in the F344/N and LEW rat strains.

Project description:The inbred Fischer (F344) and Lewis (LEW) rats, while originally developed as animal models for cancer and tissue transplantation research, have since been used to study genetic differences in a variety of physiological and behavioral endpoints. In this context, LEW rats show greater sensitivity to the aversive effects of cocaine as compared to F344 rats in a conditioned taste avoidance procedure. Like cocaine, 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") acts as a dopamine transport blocker and possesses aversive properties, making it a good candidate for assessing whether the aforementioned strain differences with cocaine would generalize to drugs with similar biochemical action. Accordingly, male F344 and LEW rats were exposed to a novel saccharin solution followed by injections of one of four doses of MDPV in a taste avoidance procedure. Over the four saccharin/MDPV pairings during conditioning, core body temperatures were also assessed. Similar to previous research, MDPV induced robust dose-dependent taste avoidance, although no effect of strain was observed. MDPV also produced hyperthermia that was independent of strain and unrelated to the conditioned taste avoidance. These findings argue for a complex influence of multiple (and likely interacting) monoaminergic systems mediating MDPV-induced taste avoidance in the two strains and suggest different mechanisms of avoidance learning for cocaine and MDPV.

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In vivo effects of abused 'bath salt' constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: drug discrimination, thermoregulation, and locomotor activity.

Project description:In recent years, synthetic analogues of naturally occurring cathinone have emerged as psychostimulant-like drugs of abuse in commercial 'bath salt' preparations. 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of these illicit products, and its structural similarities to the more well-known drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) suggest that it may have similar in vivo effects to these substances. In these studies, adult male NIH Swiss mice were trained to discriminate 0.3?mg/kg MDPV from saline, and the interoceptive effects of a range of substitution doses of MDPV, MDMA, and METH were then assessed. In separate groups of mice, surgically implanted radiotelemetry probes simultaneously monitored thermoregulatory and locomotor responses to various doses of MDPV and MDMA, as a function of ambient temperature. We found that mice reliably discriminated the MDPV training dose from saline and that cumulative doses of MDPV, MDMA, and METH fully substituted for the MDPV training stimulus. All three drugs had similar ED(50) values in this procedure. Stimulation of motor activity was observed following administration of a wide range of MDPV doses (1-30?mg/kg), and the warm ambient temperature potentiated motor activity and elicited profound stereotypy and self-injurious behavior at 30?mg/kg. In contrast, MDPV-induced hyperthermic effects were observed in only the warm ambient environment. This pattern of effects is in sharp contrast to MDMA, where ambient temperature interacts with thermoregulation, but not locomotor activity. These studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA.

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3,4-Methylenedioxypyrovalerone (MDPV) Sensing Based on Electropolymerized Molecularly Imprinted Polymers on Silver Nanoparticles and Carboxylated Multi-Walled Carbon Nanotubes.

Project description:3,4-methylenedioxypyrovalerone (MDPV) is a harmful and controlled synthetic cathinone used as a psychostimulant drug and as sport-enhancing substance. A sensor was developed for the direct analysis of MDPV by transducing its oxidation signal by means of an electropolymerized molecularly imprinted polymer (e-MIP) built in-situ on the screen-printed carbon electrode's (SPCE) surface previously covered with multi-walled carbon nanotubes (MWCNTs) and silver nanoparticles (AgNPs). Benzene-1,2-diamine was used as the functional monomer while the analyte was used as the template monomer. Each step of the sensor's development was studied by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in a solution containing ferricyanide, however no redox probe was required for the actual MDPV measurements. The interaction between the poly(o-phenylenediamine) imprinted polymer and MDPV was studied by density-functional theory (DFT) methods. The SPCE-MWCNT-AgNP-MIP sensor responded adequately to the variation of MDPV concentration. It was shown that AgNPs enhanced the electrochemical signal by around a 3-fold factor. Making use of square-wave voltammetry (SWV) the developed sensor provided a limit of detection (LOD) of 1.8 μmol L-1. The analytical performance of the proposed sensor paves the way to the development of a portable device for MDPV on-site sensing to be applied in forensic and doping analysis.

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Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells.

Project description:Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4-methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as "bath salts." These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5mM-2.5mM) for 24h. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5mM, with similar effects observed after MDPV exposures starting at 1mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1mM and disruption of the monolayer at 2.5mM. MDMA induced disruption of the endothelial monolayer from 1mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥0.5mM without vacuole formation; at 2.5mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic.

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