DOSE-RESPONSE PATTERN OF REWARD OF THREE SUBSTITUTED CATHINONES

Synthetic cathinones, sold online and in head shops as “bath salts,” have seen a tremendous increase in popularity since 2007. Consequently, the number of cathinone-related hospitalizations has increased, hitting a peak in 2011. Unfortunately, there has been very little research done regarding the behavioral effects of these drugs. The current study aimed to examine the rewarding effect of three cathinones: MDAI, flephedrone (4-FMC), and butylone. The rewarding effects were measured in a conditioned place preference test. In conditioned place preference, mice, animals regularly used as models for human behavior, are placed in one environment while under the influence of a drug, and in another while not. Before being exposed to the drug, animals are given free access to both environments, the time spent in either environment is recorded, and the environment in which less time is spent is designated the drug-paired environment. After multiple drug/nondrug environment pairings, the mice are, once again, given access to both environments and the time spent in the drug-paired environment is measured. If the time in the drug environment increases after drug exposure, the drug is said to have rewarding effects. Each of the cathinones tested produced an increase in time spent in the drug-paired environment. MDAI produced a plateau effect. Butylone produced a dose-dependent increase in time spent on the drug-paired floor. Flephedrone produced an inverted-U dose-response curve These results suggest that MDAI, flephedrone, and butylone produce rewarding effects. Given earlier findings that these compounds produced cocaine- and methamphetamine-like discriminative stimulus effects, they have a strong potential to be abused. Purpose (a): Synthetic cathinones, sold online and in head shops as “bath salts,” have seen a tremendous increase in popularity since 2007. Consequently, the number of cathinone-related hospitalizations has increased, hitting a peak in 2011. Although cathinone usage and hospitalization has decreased since the Synthetic Drug Prevention Act was passed in 2012, the drugs remain popular amongst young people and dance club frequenters. While the literature on synthetic cathinones has been steadily accumulating, behavioral data still remains sparse, especially in regards to abuse liability. The current study examined the dose-dependent rewarding effects of three substituted cathinones: MDAI (0.1, 0.3, 1, 3, 10 mg/kg), flephedrone (4-FMC, 3, 10, 30 mg/kg), and butylone (1, 3, 10 mg/kg). Methods (b): A biased conditioned place preference model of drug reward was utilized. For each drug, doses between 0.1-30 mg/kg were administered to generate a dose-response curve. Results (c): MDAI resulted in increased time on the drug-paired floor from 0.3-10 mg/kg, with 3 mg/kg yielding the largest increase. Flephedrone produced an inverted U-shaped dose-response curve with 10 mg/kg resulting in an increase in drug-paired floor time, but not 3 or 30 mg/kg. Butylone produced a dose-dependent increase in drug-paired floor time from 1 to 10 mg/kg. Conclusions (d): These results suggest that MDAI, flephedrone, and butylone produce rewarding effects. Given earlier findings that these compounds produced cocaine- and methamphetamine-like discriminative stimulus effects, they have a strong potential to be abused. Potency, efficacy, and dose-response pattern differed among the three drugs, with MDAI being the most potent, followed by butylone, then flephedrone.