Sex differences in α-pyrrolidinopentiophenone (α-PVP)-induced taste avoidance, place preference, hyperthermia and locomotor activity in rats

Pharmacol Biochem Behav. 2019 Oct:185:172762. doi: 10.1016/j.pbb.2019.172762. Epub 2019 Aug 21.

Abstract

Rationale: The majority of synthetic cathinone research has used only male subjects, and as a result there are few studies assessing the impact of biological sex on their effects.

Objectives: The current work extends the characterization of the second-generation synthetic cathinone, α-PVP, by investigating how biological sex impacts α-PVP's aversive and rewarding effects important to its use and potential abuse.

Methods: A combined conditioned taste avoidance/conditioned place preference preparation was utilized in which adult male and female Sprague Dawley rats were injected with 1.5, 3 or 6 mg/kg of racemic α-PVP or vehicle (saline) (IP). Following a 24-day washout period, rats were then tested for thermoregulatory effects of α-PVP using subcutaneous microchips to measure body temperature changes over the course of 8 h. This was followed 21 days later by assessments for α-PVP-induced locomotor activity and stereotypies over a 1-h session.

Results: Dose-dependent conditioned taste avoidance was evident in both males and females, although females displayed weaker avoidance at 3 mg/kg compared to males. Males displayed a dose-dependent conditioned place preference, while females did not form a place preference at any dose. α-PVP elicited dose- and time-dependent hyperthermia, with males displaying a faster on-set and delayed off-set compared to females. α-PVP also produced dose- and time-dependent increases in locomotor activity (F > M) and stereotypies (M > F).

Conclusions: As described, males displayed greater rewarding (as indexed by place preference conditioning) and aversive (as indexed by taste avoidance, hyperthermia and stereotypies) effects of α-PVP. Although comparisons between males and females in α-PVP self-administration have not been reported, these data suggest that males may be more likely to use the drug. The implications for sex differences in human use of α-PVP were discussed.

Keywords: Conditioned place preference; Conditioned taste avoidance; Hyperthermia; Locomotor activity; Rats; Sex; α-PVP.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Avoidance Learning / drug effects*
  • Behavior, Animal / drug effects*
  • Body Temperature / drug effects
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Conditioning, Classical
  • Dose-Response Relationship, Drug
  • Female
  • Fever / chemically induced*
  • Locomotion / drug effects*
  • Male
  • Motor Activity / drug effects
  • Pentanones / administration & dosage
  • Pentanones / pharmacology*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reward
  • Sex Factors
  • Taste / drug effects*

Substances

  • Central Nervous System Stimulants
  • Pentanones
  • Pyrrolidines
  • 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone