Katharine H Nelson1, Hayley N Manke2, Aikerim Imanalieva2, Kenner C Rice3, Anthony L Riley4. 1. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, DC 20016, USA. Electronic address: kn9165a@american.edu. 2. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, DC 20016, USA. 3. Drug Design and Synthesis Section, National Institute on Drug Abuse (NIDA), National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD 20892, USA. 4. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, DC 20016, USA. Electronic address: alriley@american.edu.
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.
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.
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