CHARACTERIZING THE NEUROCHEMICAL, PHYSIOLOGICAL AND BEHAVIORAL EFFECTS OF THE SYNTHETIC CATHINONE α-PYRROLIDINOPENTIOPHENONE (α-PVP)

α-pyrrolidinopentiophenone (α-PVP, Flakka) is a synthetic cathinone that is highly addictive and poses serious risks to the user’s mental and physical health. Despite these dangers, α-PVP remains largely unstudied. The abuse potential of a drug (i.e., its likelihood of self-administration) is dependent upon the balance of the drug’s rewarding and aversive effects and while α-PVP has begun to be studied for these effects, factors that impact them have received little attention. In this context, the goal of these experiments was to further characterize α-PVP by evaluating neurochemical (stereochemistry; Experiment 1), subject (sex; Experiment 2) and experiential (drug history; Experiment 3) factors impacting the affective properties of α-PVP. For Experiments 1A, 2, and 3, the aversive (conditioned taste avoidance (CTA), body temperature, locomotor activity and stereotypies) and rewarding (conditioned place preference (CPP)) effects of α-PVP were investigated. Experiment 1B assessed uptake inhibition of the brain amines, dopamine and norepinephrine. Results: In Experiment 1A, the S-enantiomer of α-PVP mediated the aversive effects of the racemate (in each: CTA, temperature and activity) in male Sprague Dawley (SD) rats at all doses tested. Uptake assessments (Experiment 1B) showed that the R-enantiomer was active, but less potent than the S-enantiomer and racemate. In Experiment 2, male SD rats displayed greater effects of α-PVP than females both in CPP and CTA. Males had a faster onset of temperature effects and had a longer duration of action than females, while females displayed greater locomotor activity than males (although males displayed greater stereotypies than females). In Experiment 3, ethanol pre-exposure attenuated taste avoidance but did not affect reward, which could increase abuse liability. Ethanol pre-exposure increased the locomotor effects of α-PVP (at 3 mg/kg) but had no effect on thermoregulation or stereotypies. The present data indicate that the rewarding and aversive effects of α-PVP are dependent upon its stereochemistry and significantly affected by sex and an ethanol drug history. While these findings lay initial groundwork in characterizing the aversive and rewarding effects of α-PVP, future studies assessing the effects of these properties on intravenous self-administration will be necessary to predict the abuse liability of α-PVP.