期刊
ADDICTION BIOLOGY
卷 25, 期 6, 页码 -出版社
WILEY
DOI: 10.1111/adb.12842
关键词
alpha-PVP; cardiovascular; self-administration
资金
- National Institute on Drug Abuse [Z1ADA000523, Z1ADA000532]
- National Institute of Alcohol Abuse and Alcoholism
- NATIONAL INSTITUTE ON DRUG ABUSE [ZIADA000532, ZIADA000523, ZIADA000527] Funding Source: NIH RePORTER
The synthetic cathinone alpha-pyrrolidinovalerophenone (alpha-PVP) continues to be abused despite being banned by regulatory agencies. The abused formulation of alpha-PVP is a racemic mixture consisting of two enantiomers, S-alpha-PVP and R-alpha-PVP. In this study, we investigated the neurochemical, behavioral, and cardiovascular effects of racemic alpha-PVP and its enantiomers in male rats. Racemic alpha-PVP blocked the uptake of both dopamine and norepinephrine ex vivo, but did not block the uptake of serotonin (5-HT), at their respective transporters. S-alpha-PVP was slightly more potent than racemic alpha-PVP, while R-alpha-PVP was 10 to 20 times less potent at blocking dopamine and norepinephrine uptake. In microdialysis studies, racemic and S-alpha-PVP increased extracellular dopamine levels in the nucleus accumbens, but not levels of 5-HT. Racemic and S-alpha-PVP also increased locomotor activity. When tested at the same doses, S-alpha-PVP produced larger effects than racemic alpha-PVP. R-alpha-PVP also increased extracellular dopamine levels and locomotor activity, but only at 30 times higher doses than S-alpha-PVP. Racemic and S-alpha-PVP were self-administered by rats at 0.03 mg/kg/injection, whereas R-alpha-PVP was self-administered at a 10 times higher dose. Dose-effect determinations following acquisition suggested that R-alpha-PVP was at least 30 times less potent than S-alpha-PVP. Finally, racemic and S-alpha-PVP increased blood pressure and heart rate at doses approximately 30 times less than was required for R-alpha-PVP to produce similar effects. These results show that the neurochemical, behavioral, and cardiovascular effects of racemic alpha-PVP most likely reflect the actions of S isomer.
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