Alpha-PVP Induces the Rewarding Effect via Activating Dopaminergic Neuron

J Toxicol Sci. 2017;42(5):539-543. doi: 10.2131/jts.42.539.

Abstract

A synthetic cathinone, 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP), was occasionally found in the "bath salt" type of designer drugs, as an active ingredient. It has been reported that drivers who consumed α-PVP were in an excited state and incapable of controlling their behavior, causing traffic accidents. Despite its acute excitatory effects, there is no information on the psychological dependency elicited by α-PVP use. The purpose of the present study was to clarify whether the reward pathway is activated with repeated doses of α-PVP in experimental animals. Treatment of male C57BL/6j mice with α-PVP (25 mg/kg, i.p.), once a day, for 3 days significantly increased the conditioned place preference scores. Therefore, repeated doses of α-PVP were shown to induce palatability in mice. α-PVP increases extracellular dopamine levels in the nucleus accumbens shell immediately after administration. The number of cells immunopositive for phosphorylated cAMP-regulatory element binding protein (CREB) was significantly increased in the α-PVP-treated mice in our study. These results indicate that the administration of α-PVP activates the phosphorylation of CREB in the nucleus accumbens shell. Our results suggest that α-PVP stimulates the reward pathway by increasing the extracellular dopamine levels and CREB phosphorylation in the nucleus accumbens shell, eventually causing positive reinforcement in mice.

Keywords: 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP); CREB; Conditioned place preference; Immunohistochemistry; Microdialysis.

MeSH terms

  • Animals
  • Conditioning, Psychological / drug effects
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Designer Drugs / administration & dosage*
  • Designer Drugs / adverse effects*
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism*
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Nucleus Accumbens / metabolism
  • Pentanones / administration & dosage*
  • Pentanones / adverse effects*
  • Phosphorylation / drug effects
  • Pyrrolidines / administration & dosage*
  • Pyrrolidines / adverse effects*
  • Reinforcement, Psychology
  • Reward*

Substances

  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Designer Drugs
  • Pentanones
  • Pyrrolidines
  • 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone
  • Dopamine