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

• Published in: Pharmacology, biochemistry and behavior Vol. 185; p. 172762
• Main Authors: Nelson, Katharine H., Manke, Hayley N., Imanalieva, Aikerim, Rice, Kenner C., Riley, Anthony L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Animals; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Body Temperature - drug effects; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Conditioned place preference; Conditioned taste avoidance; Conditioning, Classical; Dose-Response Relationship, Drug; Female; Fever - chemically induced; Hyperthermia; Locomotion - drug effects; Locomotor activity; Male; Motor Activity - drug effects; Pentanones - administration & dosage; Pentanones - pharmacology; Pyrrolidines - administration & dosage; Pyrrolidines - pharmacology; Rats; Rats, Sprague-Dawley; Reward; Sex; Sex Factors; Taste - drug effects; α-PVP; Conditioned taste avoidance; α-PVP; Conditioned place preference; Sex; Rats; Hyperthermia; Locomotor activity
• ISSN: 0091-3057; 1873-5177; 1873-5177
• DOI: 10.1016/j.pbb.2019.172762

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. 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. 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. 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). 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. •Drug use and abuse are a function of a balance of aversive and rewarding effects; factors such as sex impact this balance.•Males showed greater α-PVP induced taste avoidance than females; dose-dependent taste avoidance was evident in both sexes.•Significant differences emerged in α-PVP’s rewarding effects with only males displaying conditioned place preferences.•With α-PVP-induced hyperthermia, males showed a faster on-set and delayed off-set compared to females.•Females displayed greater locomotor activity following α-PVP with increased stereotypies in males compared to females.