Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives

Synthetic cathinones, often sold as "bath salts," are a popular class of recreational drugs used as quasi-legal alternatives to cocaine, methamphetamine, and methylenedioxymethamphetamine. The increased prevalence and health consequences of synthetic cathinone use has prompted regulatory agencies to control a number of these compounds; however, a broad class of analogous compounds known as the second-generation cathinones has been brought to the market to take the place of the banned synthetic cathinone derivatives. The current study aims to characterize the behavioral pharmacology of three pyrrolidinylated second-generation cathinones: 4-methyl-alpha-pyrrolidinopropiophenone (4'-MePPP), alpha-pyrrolidinopropiobutiophenone (alpha-PBP), and alpha-pyrrolidinopentiophenone (alpha-PVP). Locomotor activity was tested in mice over an 8-hour period. The discriminative stimulus effects of these compounds were tested in rats trained to discriminate either cocaine or methamphetamine. The rewarding effects of these drugs were assessed in mice using conditioned place preference. Both alpha-PBP and alpha-PVP produced long-lasting increases in locomotor activity across a wide range of doses, whereas 4'-MePPP produced locomotor stimulation only at 30 mg/kg. Both alpha-PBP and alpha-PVP fully substituted for the discriminative stimulus effects of both cocaine and methamphetamine, whereas 4'-MePPP substituted fully for the discriminative stimulus effects of methamphetamine only. Both alpha-PBP and alpha-PVP produced conditioned place preference in an inverted U-shaped dose effect, whereas 4'-MePPP did not produce conditioned place preference. These findings suggest that alpha-PBP and alpha-PVP are likely to be recreationally used and have potential for addiction and abuse, but 4'-MePPP may not.