Binge-like Acquisition of α-pyrrolidinopentiophenone (α-PVP) Self-Administration in Female Rats

Abstract

Rationale: The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) recently drew attention due to reports of violent and/or bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of selfadministration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone.Objectives: The binge-like acquisition pattern appeared to be novel for rat IVSA, thus the present study was designed to determine if this effect generalizes to IVSA of α-PVP in female rats.Methods: Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers that contained an activity wheel. Groups (N=12 per group) of animals were trained with the wheels fixed (No-Wheel group) or free to move (Wheel group). Following acquisition, the groups were subjected to a wheel-access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. Results:Half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity declined as acquisition progressed in the Wheel group and was much lower in the No-Wheel group in the wheel switch post-acquisition. Doseeffect curves were similar for binge/no binge subgroups and were not altered with wheel access during the dose-substitution.Conclusions: This confirms the high reinforcer efficacy of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.peer-reviewed)

Stereoselective neurochemical, behavioral, and cardiovascular effects of α‐pyrrolidinovalerophenone enantiomers in male rats

“…The effects of α-PVP on temperature were small and failed to reach significance, although racemic α-PVP tended to increase body temperature. Our results agree with the findings of Nelson et al, 26 Finally, confirming what others have shown for racemic α-PVP, 20,24,[28][29][30][31][32][33] rats self-administered α-PVP at doses similar to racemic MDPV. 45 Self-administration was acquired rapidly with α-PVP, and the drug produced a typical inverted U-shaped dose-effect function comparable with other psychomotor stimulants.…”

“…Finally, confirming what others have shown for racemic α‐PVP, 20,24–24,28–33 rats self‐administered α‐PVP at doses similar to racemic MDPV 45 . Self‐administration was acquired rapidly with α‐PVP, and the drug produced a typical inverted U‐shaped dose‐effect function comparable with other psychomotor stimulants.…”

“…It produces place preference in mice and rats, 21,22,26 and it reduces intracranial self-stimulation thresholds 27 and is self-administered by rats. 20,24,[28][29][30][31][32][33] α-PVP also generalizes to other psychomotor stimulants in drug discrimination procedures carried out in rodents and monkeys. 22,34,35 MDPV has two enantiomers, R and S, based on absolute configuration.…”

“…α‐PVP has effects that are predictive of its abuse in humans. It produces place preference in mice and rats, 21–22,26 and it reduces intracranial self‐stimulation thresholds 27 and is self‐administered by rats 20,24–24,28–33 . α‐PVP also generalizes to other psychomotor stimulants in drug discrimination procedures carried out in rodents and monkeys 22,34–35 …”

Distinguishing the behavioral potencies of α-pyrrolidino-phenone cathinone stimulants

“…This class of pyrrolidino-phenone cathinone compounds are dopamine transporter (DAT) and norepinephrine transporter (NET) selective (over the serotonin transporter; SERT) inhibitors which do not serve as substrates/releasers (Eshleman et al, 2017) as do commonly recognized amphetamineclass stimulants such as methamphetamine and 3,4methylenedioxy-methamphetamine and even some of the cathinones such as mephedrone or methylone (Simmler et al, 2013;Simmler et al, 2014). Cocaine is a classic non-substrate monoamine transporter inhibitor psychomotor stimulant, thus it is unsurprisingly that MDPV (Aarde et al, 2013;Aarde et al, 2015b;Gannon et al, 2017b;Watterson et al, 2014) and α-PVP (Aarde et al, 2015a;Gannon et al, 2017a;Gannon et al, 2017b;Huskinson et al, 2017;Javadi-Paydar et al, 2018a;Schindler et al, 2019) are highly effective reinforcers in animal models. MDPV and a-PVP appear to have similar potency as reinforcers (Aarde et al, 2015a), consistent with similar potencies as DAT inhibitors in vivo (Gannon et al, 2018).…”