Cocaine-Like Discriminative Stimulus Effects of Mephedrone and Naphyrone in Mice

In recent years, commercial bath salts products containing synthetic cathinone analogues have emerged as illicit drugs of abuse. These cathinones are structurally similar to the psychostimulants 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH), and produce their effects via interactions with monoamine transporters, where smaller compounds (e.g., mephedrone) are amphetamine-like monoamine releasers, while the structurally larger compounds (e.g., naphyrone) are cocaine-like monoamine reuptake inhibitors. Individual cathinones also differ from one another with respect to selectivity among the three monoamine transporters.

This study was designed to assess the cocaine-like interoceptive effects of synthetic cathinone analogues functioning as passive monoamine reuptake inhibitors (naphyrone) or as releasers (mephedrone) in mice in order to compare effectiveness (degree of substitution) and potency with positive control psychostimulants cocaine, METH, and MDMA.

In the present study, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with METH, MDMA, mephedrone, naphyrone, and morphine were performed.

Mice reliably discriminated the cocaine training dose from saline, and METH, MDMA, mephedrone, and naphyrone all elicited full cocaine-like responding, while morphine did not. Potency differences were observed such that METH was most potent, while mephedrone, cocaine, MDMA, and naphyrone exhibited roughly equivalent potency.

These data confirm that interaction with DAT is an important component of cocaine-like discriminative stimulus effects, and suggest that synthetic cathinones likely elicit psychostimulant-like abuse-related effects.