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):4631. doi: 10.3390/ijms21134631.


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.

Keywords: abuse potential; conditioned place preference; designer drugs; phencyclidine (PCP) derivatives; self-administration.

MeSH terms

  • Animals
  • Behavior, Addictive / physiopathology
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleus Accumbens / metabolism
  • Phencyclidine / analogs & derivatives*
  • Phencyclidine / metabolism
  • Phencyclidine / pharmacology*
  • Phencyclidine Abuse / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / metabolism
  • Reinforcement, Psychology
  • Reward
  • Self Administration


  • Dopamine Plasma Membrane Transport Proteins
  • Proto-Oncogene Proteins c-fos
  • Receptors, Dopamine D1
  • Phencyclidine
  • Dopamine