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Open AccessArticle

The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents

1
Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea
2
Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, Seoul 01795, Korea
3
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
4
Department of Psychology and Neuroscience, Brigham Young University, Provo, UT 84602, USA
5
Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea
*
Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
Int. J. Mol. Sci. 2020, 21(13), 4631; https://doi.org/10.3390/ijms21134631
Received: 14 May 2020 / Revised: 19 June 2020 / Accepted: 27 June 2020 / Published: 29 June 2020
The dissociative anesthetic phencyclidine (PCP) and PCP derivatives, including 4′-F-PCP, are illegally sold and abused worldwide for recreational and non-medical uses. The psychopharmacological properties and abuse potential of 4′-F-PCP have not been fully characterized. In this study, we evaluated the psychomotor, rewarding, and reinforcing properties of 4′-F-PCP using the open-field test, conditioned place preference (CPP), and self-administration paradigms in rodents. Using Western immunoblotting, we also investigated the expression of dopamine (DA)-related proteins and DA-receptor-mediated downstream signaling cascades in the nucleus accumbens (NAc) of 4′-F-PCP-self-administering rats. Intraperitoneal administration of 10 mg/kg 4′-F-PCP significantly increased locomotor and rearing activities and increased CPP in mice. Intravenous administration of 1.0 mg/kg/infusion of 4′-F-PCP significantly enhanced self-administration during a 2 h session under fixed ratio schedules, showed a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement, and significantly altered the expression of DA transporter and DA D1 receptor in the NAc of rats self-administering 1.0 mg/kg 4′-F-PCP. Additionally, the expression of phosphorylated (p) ERK, pCREB, c-Fos, and FosB/ΔFosB in the NAc was significantly enhanced by 1.0 mg/kg 4′-F-PCP self-administration. Taken together, these findings suggest that 4′-F-PCP has a high potential for abuse, given its robust psychomotor, rewarding, and reinforcing properties via activation of DAergic neurotransmission and the downstream signaling pathways in the NAc. View Full-Text
Keywords: abuse potential; conditioned place preference; designer drugs; self-administration; phencyclidine (PCP) derivatives abuse potential; conditioned place preference; designer drugs; self-administration; phencyclidine (PCP) derivatives
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Ryu, I.S.; Kim, O.-H.; Lee, Y.E.; Kim, J.S.; Li, Z.-H.; Kim, T.W.; Lim, R.-N.; Lee, Y.J.; Cheong, J.H.; Kim, H.J.; Lee, Y.S.; Steffensen, S.C.; Lee, B.H.; Seo, J.-W.; Jang, E.Y. The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents. Int. J. Mol. Sci. 2020, 21, 4631.

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