Locomotor activity and discriminative stimulus effects of a novel series of synthetic cathinone analogs in mice and rats

Rationale Recent years have seen an increase in the recreational use of novel, synthetic psychoactive substances. There are little or no data on the abuse liability of many of the newer compounds. Objectives The current study investigated the discriminative stimulus and locomotor effects of a series of synthetic analogs of cathinone: alpha-pyrrolidinopropiophenone (alpha-PPP), a-pyrrolidinohexiophenone (alpha-PHP), apyrrolidinop entiothiophenone (alpha-PVT), 3, 4 methylenedioxybutiophenone (MDPBP), and ethylone. Methods Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from vehicle. Results Each of the compounds produced an inverted-U doseeffect on locomotor activity. Maximal effects were similar among the test compounds, but potencies varied with relative potencies of MDPBP > alpha-PPP = alpha-PHP > ethylone > alpha-PVT. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine. a-PPP, a-PHP, and ethylone fully substituted for cocaine. a-PVT produced a maximum of 50% cocaine-appropriate responding, and MDPBP produced an inverted-U-shaped dose-effect curve with maximum effects of 67%. Conclusions These data provide initial evidence that these structurally similar, emerging novel psychoactive substances demonstrate potential for abuse and may be utilized for their stimulant-like effects, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of the classical psychostimulants cocaine and/or methamphetamine.