4-MeO-PCP and 3-MeO-PCMo, new dissociative drugs, produce rewarding and reinforcing effects through activation of mesolimbic dopamine pathway and alteration of accumbal CREB, deltaFosB, and BDNF levels

Abiero, Arvie; Botanas, Chrislean Jun; Custodio, Raly James Perez; Sayson, Leandro Val; Kim, Mi-Kyung; Lee, Hyun Jun; Kim, Hee Jin; Lee, Kun Won; Jeong, Youngdo; Seo, Joung‐Wook; Ryu, In Soo; Lee, Yong Sup; Cheong, Jae Hoon

doi:10.1007/s00213-019-05412-y

Cited by 18 publications

(35 citation statements)

References 62 publications

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“…The CPP is another classic animal model used to evaluate the rewarding effect of contextual stimuli associated with exposure to addictive drugs [14,15]. Previous studies demonstrated that repeated administration of PCP or PCP derivatives produced a positive preference [18][19][20]. Consistent with these findings, our results demonstrated that 4 -F-PCP at a dose of 10 mg/kg produced a significant increase in preference in mice.…”

Section: Discussionsupporting

confidence: 89%

“…In previous studies, PCP and PCP derivatives produced robust increases in locomotor activity [17,18] and CPP in rodents [18][19][20]. Moreover, PCP and PCP derivatives were significantly self-administered in rodent and primate animal models [18,[20][21][22]. These findings suggest that PCP and PCP derivatives not only cause psychotomimetic effects [2], but also produce psychological dependence with chronic use, due to their reward potential.…”

Section: Introductionmentioning

confidence: 71%

“…Drug-induced increases in psychomotor activities are closely related to hyperstimulation of the mesolimbic DAergic reward system [26]. Previous studies reported that administration of PCP or PCP derivatives increased locomotor and rotational activities in a dose-dependent manner [17,18,27,28], and its psychomotor effects were blocked by antagonism of DAD1R activity [17]. Similarly, administration of ketamine or methoxetamine, a kind of PCP-like substance, also increased psychomotor responses in a dose-dependent manner in rodents [29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…The structure-activity relationship studies demonstrated that PCP derivatives can act as DA reuptake inhibitors due to their structural similarity to PCP, thereby increasing extracellular DA levels in the brain [9,10,19]. For example, Abiero et al demonstrated that 4-MeO-PCP and 3-MeO-PCMo, which are structurally similar to PCP, increased DA concentration in the NAc of mice [18]. Based on these findings, we speculate that 4 -F-PCP enhances psychomotor activities and produces the preference via increased DA levels in the NAc.…”

Section: Discussionmentioning

confidence: 99%

“…drug self-administration paradigms [14][15][16]. In previous studies, PCP and PCP derivatives produced robust increases in locomotor activity [17,18] and CPP in rodents [18][19][20]. Moreover, PCP and PCP derivatives were significantly self-administered in rodent and primate animal models [18,[20][21][22].…”

Section: Introductionmentioning

confidence: 98%

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

Ryu

Kim

Lee

et al. 2020

IJMS

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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.

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