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The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents
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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369973/ https://www.ncbi.nlm.nih.gov/pubmed/32610694 http://dx.doi.org/10.3390/ijms21134631 |
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author | Ryu, In Soo Kim, Oc-Hee Lee, Young Eun Kim, Ji Sun Li, Zhan-Hui Kim, Tae Wan Lim, Ri-Na Lee, Young Ju Cheong, Jae Hoon Kim, Hee Jin Lee, Yong Sup Steffensen, Scott C. Lee, Bong Hyo Seo, Joung-Wook Jang, Eun Young |
author_facet | Ryu, In Soo Kim, Oc-Hee Lee, Young Eun Kim, Ji Sun Li, Zhan-Hui Kim, Tae Wan Lim, Ri-Na Lee, Young Ju Cheong, Jae Hoon Kim, Hee Jin Lee, Yong Sup Steffensen, Scott C. Lee, Bong Hyo Seo, Joung-Wook Jang, Eun Young |
author_sort | Ryu, In Soo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7369973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73699732020-07-21 The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents Ryu, In Soo Kim, Oc-Hee Lee, Young Eun Kim, Ji Sun Li, Zhan-Hui Kim, Tae Wan Lim, Ri-Na Lee, Young Ju Cheong, Jae Hoon Kim, Hee Jin Lee, Yong Sup Steffensen, Scott C. Lee, Bong Hyo Seo, Joung-Wook Jang, Eun Young Int J Mol Sci Article 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. MDPI 2020-06-29 /pmc/articles/PMC7369973/ /pubmed/32610694 http://dx.doi.org/10.3390/ijms21134631 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ryu, In Soo Kim, Oc-Hee Lee, Young Eun Kim, Ji Sun Li, Zhan-Hui Kim, Tae Wan Lim, Ri-Na Lee, Young Ju Cheong, Jae Hoon Kim, Hee Jin Lee, Yong Sup Steffensen, Scott C. Lee, Bong Hyo Seo, Joung-Wook Jang, Eun Young The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents |
title | The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents |
title_full | The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents |
title_fullStr | The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents |
title_full_unstemmed | The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents |
title_short | The Abuse Potential of Novel Synthetic Phencyclidine Derivative 1-(1-(4-Fluorophenyl)Cyclohexyl)Piperidine (4′-F-PCP) in Rodents |
title_sort | abuse potential of novel synthetic phencyclidine derivative 1-(1-(4-fluorophenyl)cyclohexyl)piperidine (4′-f-pcp) in rodents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369973/ https://www.ncbi.nlm.nih.gov/pubmed/32610694 http://dx.doi.org/10.3390/ijms21134631 |
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