Alpha-PVP induces the rewarding effect via activating dopaminergic neuron

摘要

A synthetic cathinone, 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (alpha-PVP), was occasionally found in the "bath salt" type of designer drugs, as an active ingredient. It has been reported that drivers who consumed alpha-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 alpha-PVP use. The purpose of the present study was to clarify whether the reward pathway is activated with repeated doses of alpha-PVP in experimental animals. Treatment of male C57BL/6j mice with alpha-PVP (25 mg/kg, i.p.), once a day, for 3 days significantly increased the conditioned place preference scores. Therefore, repeated doses of alpha-PVP were shown to induce palatability in mice. alpha-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 alpha-PVP-treated mice in our study. These results indicate that the administration of alpha-PVP activates the phosphorylation of CREB in the nucleus accumbens shell. Our results suggest that alpha-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.