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The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents.
Int J Mol Sci. 2020 Jun 29; 21(13)IJ

Abstract

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.

Authors+Show Affiliations

Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, Seoul 01795, Korea.Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, Seoul 01795, Korea.Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea.Department of Psychology and Neuroscience, Brigham Young University, Provo, UT 84602, USA.Department of Acupuncture, Moxibustion and Acupoint, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.Pharmacology and Drug Abuse Research Group, Korea Institute of Toxicology, Daejeon 34114, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32610694

Citation

Ryu, In Soo, et al. "The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents." International Journal of Molecular Sciences, vol. 21, no. 13, 2020.
Ryu IS, Kim OH, Lee YE, et al. 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(13).
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. (2020). The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents. International Journal of Molecular Sciences, 21(13). https://doi.org/10.3390/ijms21134631
Ryu IS, et al. The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents. Int J Mol Sci. 2020 Jun 29;21(13) PubMed PMID: 32610694.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4'-F-PCP) in Rodents. AU - Ryu,In Soo, AU - Kim,Oc-Hee, AU - Lee,Young Eun, AU - Kim,Ji Sun, AU - Li,Zhan-Hui, AU - Kim,Tae Wan, AU - Lim,Ri-Na, AU - Lee,Young Ju, AU - Cheong,Jae Hoon, AU - Kim,Hee Jin, AU - Lee,Yong Sup, AU - Steffensen,Scott C, AU - Lee,Bong Hyo, AU - Seo,Joung-Wook, AU - Jang,Eun Young, Y1 - 2020/06/29/ PY - 2020/05/14/received PY - 2020/06/19/revised PY - 2020/06/27/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - abuse potential KW - conditioned place preference KW - designer drugs KW - phencyclidine (PCP) derivatives KW - self-administration JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 13 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32610694/The_Abuse_Potential_of_Novel_Synthetic_Phencyclidine_Derivative_1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine_(4'-F-PCP)_in_Rodents L2 - https://www.mdpi.com/resolver?pii=ijms21134631 DB - PRIME DP - Unbound Medicine ER -
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