The dopaminergic alterations induced by 4-F-PCP and 4-Keto-PCP may enhance their drug-induced rewarding and reinforcing effects: Implications for abuse.

Ortiz, DM; Custodio, RJP; Abiero, A; Botanas, CJ; Sayson, LV; Kim, M; Lee, HJ; Kim, HJ; Jeong, Y; Yoon, S; Lee, YS; Cheong, JH

The dopaminergic alterations induced by 4-F-PCP and 4-Keto-PCP may enhance their drug-induced rewarding and reinforcing effects: Implications for abuse.

Ortiz, DM Custodio, RJP Abiero, A Botanas, CJ Sayson, LV Kim, M Lee, HJ Kim, HJ Jeong, Y Yoon, S Lee, YS Cheong, JH

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Addiction Biology, 2021, 26, (4), pp. 1-10
Issue Date:: 2021-01-01

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Field	Value	Language
dc.contributor.author	Ortiz, DM
dc.contributor.author	Custodio, RJP
dc.contributor.author	Abiero, A
dc.contributor.author	Botanas, CJ
dc.contributor.author	Sayson, LV
dc.contributor.author	Kim, M
dc.contributor.author	Lee, HJ
dc.contributor.author	Kim, HJ
dc.contributor.author	Jeong, Y
dc.contributor.author	Yoon, S
dc.contributor.author	Lee, YS
dc.contributor.author	Cheong, JH
dc.date.accessioned	2022-02-15T02:44:41Z
dc.date.available	2020-10-07
dc.date.available	2022-02-15T02:44:41Z
dc.date.issued	2021-01-01
dc.identifier.citation	Addiction Biology, 2021, 26, (4), pp. 1-10
dc.identifier.issn	1355-6215
dc.identifier.issn	1369-1600
dc.identifier.uri	http://hdl.handle.net/10453/154519
dc.description.abstract	Novel psychoactive substances remain the popular recreational drugs of use over the years. They continue to bypass government restrictions due to their synthesis and modifications. Recent additions to the lists are the 4-F-PCP and 4-Keto-PCP, analogs of the drug phencyclidine (PCP) known to induce adverse effects and abuse potential. However, studies on the abuse potential of 4-F-PCP and 4-Keto-PCP remain scarce. The rewarding and reinforcing effects of the drugs were assessed using conditioned place preference (CPP), self-administration, and locomotor sensitization tests. Dopamine (DA) receptor antagonists (SCH23390 and haloperidol) were administered during CPP to evaluate the involvement of the mesolimbic dopaminergic system. DA-related protein expression in the nucleus accumbens (NAcc) and ventral tegmental area (VTA) was measured. Additionally, phosphorylated cyclic-adenosine monophosphate-activated protein (AMP) response element-binding (p-CREB) protein, deltaFosB (∆FosB), and brain-derived neurotrophic factor (BDNF) protein levels in the NAcc were measured to assess the addiction neural plasticity effect of the drugs. Both 4-F-PCP and 4-Keto-PCP-induced CPP and self-administration; however, only 4-F-PCP elicited locomotor sensitization. Treatment with DA receptor antagonists (SH23390 and haloperidol) inhibited the 4-F- and 4-Keto-induced CPP. Both substances altered the levels of DA receptor D1 (DRD1), thyroxine hydroxylase (TH), DA receptor D2 (DRD2), p-CREB, ∆FosB, and BDNF. The results suggest that 4-F-PCP and 4-Keto-PCP may induce abuse potential in rodents via alterations in dopaminergic system accompanied by addiction neural plasticity.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Addiction Biology
dc.relation.isbasedon	10.1111/adb.12981
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences
dc.subject.classification	Substance Abuse
dc.subject.mesh	Animals
dc.subject.mesh	Conditioning, Operant
dc.subject.mesh	Dopamine
dc.subject.mesh	Dopamine Antagonists
dc.subject.mesh	Illicit Drugs
dc.subject.mesh	Mice
dc.subject.mesh	Neuronal Plasticity
dc.subject.mesh	Nucleus Accumbens
dc.subject.mesh	Rats
dc.subject.mesh	Reinforcement, Psychology
dc.subject.mesh	Reward
dc.subject.mesh	Self Administration
dc.subject.mesh	Synthetic Drugs
dc.subject.mesh	Ventral Tegmental Area
dc.subject.mesh	Ventral Tegmental Area
dc.subject.mesh	Nucleus Accumbens
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Rats
dc.subject.mesh	Dopamine
dc.subject.mesh	Dopamine Antagonists
dc.subject.mesh	Self Administration
dc.subject.mesh	Conditioning, Operant
dc.subject.mesh	Reward
dc.subject.mesh	Neuronal Plasticity
dc.subject.mesh	Synthetic Drugs
dc.subject.mesh	Reinforcement, Psychology
dc.subject.mesh	Illicit Drugs
dc.title	The dopaminergic alterations induced by 4-F-PCP and 4-Keto-PCP may enhance their drug-induced rewarding and reinforcing effects: Implications for abuse.
dc.type	Journal Article
utslib.citation.volume	26
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
utslib.for	17 Psychology and Cognitive Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-02-15T02:44:34Z
pubs.issue	4
pubs.publication-status	Published
pubs.volume	26
utslib.citation.issue	4

Abstract:

Novel psychoactive substances remain the popular recreational drugs of use over the years. They continue to bypass government restrictions due to their synthesis and modifications. Recent additions to the lists are the 4-F-PCP and 4-Keto-PCP, analogs of the drug phencyclidine (PCP) known to induce adverse effects and abuse potential. However, studies on the abuse potential of 4-F-PCP and 4-Keto-PCP remain scarce. The rewarding and reinforcing effects of the drugs were assessed using conditioned place preference (CPP), self-administration, and locomotor sensitization tests. Dopamine (DA) receptor antagonists (SCH23390 and haloperidol) were administered during CPP to evaluate the involvement of the mesolimbic dopaminergic system. DA-related protein expression in the nucleus accumbens (NAcc) and ventral tegmental area (VTA) was measured. Additionally, phosphorylated cyclic-adenosine monophosphate-activated protein (AMP) response element-binding (p-CREB) protein, deltaFosB (∆FosB), and brain-derived neurotrophic factor (BDNF) protein levels in the NAcc were measured to assess the addiction neural plasticity effect of the drugs. Both 4-F-PCP and 4-Keto-PCP-induced CPP and self-administration; however, only 4-F-PCP elicited locomotor sensitization. Treatment with DA receptor antagonists (SH23390 and haloperidol) inhibited the 4-F- and 4-Keto-induced CPP. Both substances altered the levels of DA receptor D1 (DRD1), thyroxine hydroxylase (TH), DA receptor D2 (DRD2), p-CREB, ∆FosB, and BDNF. The results suggest that 4-F-PCP and 4-Keto-PCP may induce abuse potential in rodents via alterations in dopaminergic system accompanied by addiction neural plasticity.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/154519