Binge-like acquisition of α-pyrrolidinopentiophenone (α-PVP) self-administration in female rats

Abstract

Rationale

The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with 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 self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone.

Objectives

The binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought 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 containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next 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

Approximately 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 was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution.

Conclusion

This confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.

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Acknowledgements

This work was funded by support from the US Public Health Service National Institutes of Health (R01DA042211) which had no direct input on the design, conduct, analysis, or publication of the findings. Conception and securing funding for the project: MAT, TJD; study design: MAT, MJ-P, JDN; data collection and initial analysis: MJ-P, ELH, YG, SAV, KMC, JDN; statistical analysis and figure creation: MAT; manuscript drafting: MAT, MJ-P. All authors have read and approved the manuscript. The authors declare no competing financial interests. This is manuscript #29574 from The Scripps Research Institute.

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Correspondence to Michael A. Taffe.

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All experimental procedures were conducted under protocols approved by the Institutional Care and Use Committees of The Scripps Research Institute and in a manner consistent with the Guide for the Care and Use of Laboratory Animals (National Research Council (U.S.). Committee for the Update of the Guide for the Care and Use of Laboratory Animals. et al. 2011).

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Javadi-Paydar, M., Harvey, E.L., Grant, Y. et al. Binge-like acquisition of α-pyrrolidinopentiophenone (α-PVP) self-administration in female rats. Psychopharmacology 235, 2447–2457 (2018). https://doi.org/10.1007/s00213-018-4943-3

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Keywords

  • Reward
  • “Bath salts”
  • Psychostimulants
  • Synthetic drugs
  • Wheel running