Arvie Abiero1, Chrislean Jun Botanas1, Raly James Custodio1, Leandro Val Sayson1, Mikyung Kim1, Hyun Jun Lee1, Hee Jin Kim1, Kun Won Lee2, Youngdo Jeong2, Joung-Wook Seo3, In Soo Ryu3, Yong Sup Lee4, Jae Hoon Cheong5,6. 1. Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea. 2. Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea. 3. Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon, 305-343, Republic of Korea. 4. Medicinal Chemistry Laboratory, Department of Pharmacy & Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea. kyslee@khu.ac.kr. 5. Uimyung Research Institute for Neuroscience, College of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea. cheongjh@syu.ac.kr. 6. School of Pharmacy, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do, 54896, Republic of Korea. cheongjh@syu.ac.kr.
Abstract
RATIONALE: A high number of synthetic dissociative drugs continue to be available through online stores, leading to their misuse. Recent inclusions in this category are 4-MeO-PCP and 3-MeO-PCMo, analogs of phencyclidine. Although the dissociative effects of these drugs and their recreational use have been reported, no studies have investigated their abuse potential. OBJECTIVES: To examine their rewarding and reinforcing effects and explore the mechanistic correlations. METHODS: We used conditioned place preference (CPP), self-administration, and locomotor sensitization tests to assess the rewarding and reinforcing effects of the drugs. We explored their mechanism of action by pretreating dopamine receptor (DR) D1 antagonist SCH23390 and DRD2 antagonist haloperidol during CPP test and investigated the effects of 4-MeO-PCP and 3-MeO-PCMo on dopamine-related proteins in the ventral tegmental area and nucleus accumbens. We also measured the levels of dopamine, phosphorylated cyclic-AMP response element-binding (p-CREB) protein, deltaFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens. Additionally, we examined the effects of both drugs on brain wave activity using electroencephalography. RESULTS: While both 4-MeO-PCP and 3-MeO-PCMo induced CPP and self-administration, only 4-MeO-PCP elicited locomotor sensitization. SCH23390 and haloperidol inhibited the acquisition of drug CPP. 4-MeO-PCP and 3-MeO-PCMo altered the levels of tyrosine hydroxylase, DRD1, DRD2, and dopamine, as well as that of p-CREB, deltaFosB, and BDNF. All drugs increased the delta and gamma wave activity, whereas pretreatment with SCH23390 and haloperidol inhibited it. CONCLUSION: Our results indicate that 4-MeO-PCP and 3-MeO-PCMo induce rewarding and reinforcing effects that are probably mediated by the mesolimbic dopamine system, suggesting an abuse liability in humans.
RATIONALE: A high number of synthetic dissociative drugs continue to be available through online stores, leading to their misuse. Recent inclusions in this category are 4-MeO-PCP and 3-MeO-PCMo, analogs of phencyclidine. Although the dissociative effects of these drugs and their recreational use have been reported, no studies have investigated their abuse potential. OBJECTIVES: To examine their rewarding and reinforcing effects and explore the mechanistic correlations. METHODS: We used conditioned place preference (CPP), self-administration, and locomotor sensitization tests to assess the rewarding and reinforcing effects of the drugs. We explored their mechanism of action by pretreating dopamine receptor (DR) D1 antagonist SCH23390 and DRD2 antagonist haloperidol during CPP test and investigated the effects of 4-MeO-PCP and 3-MeO-PCMo on dopamine-related proteins in the ventral tegmental area and nucleus accumbens. We also measured the levels of dopamine, phosphorylated cyclic-AMP response element-binding (p-CREB) protein, deltaFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens. Additionally, we examined the effects of both drugs on brain wave activity using electroencephalography. RESULTS: While both 4-MeO-PCP and 3-MeO-PCMo induced CPP and self-administration, only 4-MeO-PCP elicited locomotor sensitization. SCH23390 and haloperidol inhibited the acquisition of drug CPP. 4-MeO-PCP and 3-MeO-PCMo altered the levels of tyrosine hydroxylase, DRD1, DRD2, and dopamine, as well as that of p-CREB, deltaFosB, and BDNF. All drugs increased the delta and gamma wave activity, whereas pretreatment with SCH23390 and haloperidol inhibited it. CONCLUSION: Our results indicate that 4-MeO-PCP and 3-MeO-PCMo induce rewarding and reinforcing effects that are probably mediated by the mesolimbic dopamine system, suggesting an abuse liability in humans.
Authors: Ike dela Peña; Seo Young Yoon; Jong Chan Lee; June Bryan dela Peña; Aee Ree Sohn; Jong Hoon Ryu; Chan Young Shin; Jae Hoon Cheong Journal: Psychopharmacology (Berl) Date: 2011-11-17 Impact factor: 4.530
Authors: Yan Du; Li Du; Jie Cao; Christian Hölscher; Yongming Feng; Hongliang Su; Yujin Wang; Ke-Ming Yun Journal: Behav Brain Res Date: 2016-10-03 Impact factor: 3.332
Authors: Irina N Krasnova; Margarit Chiflikyan; Zuzana Justinova; Michael T McCoy; Bruce Ladenheim; Subramaniam Jayanthi; Cynthia Quintero; Christie Brannock; Chanel Barnes; Jordan E Adair; Elin Lehrmann; Firas H Kobeissy; Mark S Gold; Kevin G Becker; Steven R Goldberg; Jean Lud Cadet Journal: Neurobiol Dis Date: 2013-05-30 Impact factor: 5.996
Authors: In Soo Ryu; Oc-Hee Kim; Young Eun Lee; Ji Sun Kim; Zhan-Hui Li; Tae Wan Kim; Ri-Na Lim; Young Ju Lee; Jae Hoon Cheong; Hee Jin Kim; Yong Sup Lee; Scott C Steffensen; Bong Hyo Lee; Joung-Wook Seo; Eun Young Jang Journal: Int J Mol Sci Date: 2020-06-29 Impact factor: 5.923