Behavioral economic analysis of the reinforcing effects of "bath salts" mixtures: studies with MDPV, methylone, and caffeine in male Sprague-Dawley rats.

Rationale: "Bath salts" preparations often contain combinations of synthetic cathinones (e.g., 3,4-methylenedioxymethcathinone [methylone], 3,4-methylenedioxypyrovalerone [MDPV]), and caffeine, and evidence suggests that mixtures of synthetic cathinones and caffeine (e.g., MDPV + caffeine or methylone + caffeine) can be more potent and/or effective reinforcers than predicted for an additive interaction.

Objective: To use demand curve analyses to compare the reinforcing effectiveness of MDPV and methylone to mixtures of MDPV + caffeine and methylone + caffeine.

Methods: Male Sprague-Dawley rats acquired methylone self-administration (0.32 mg/kg/inf) under a fixed ratio (FR) 1 schedule of reinforcement and generated full dose-response curves for methylone (0.01-1 mg/kg/inf) under an FR5 schedule of reinforcement. Demand curves were then obtained for methylone, MDPV, caffeine, and methylone + caffeine and MDPV + caffeine mixtures by increasing the FR across sessions according to the following series: 3, 10, 18, 32, 56, 100, 178, etc. RESULTS: Self-administration of methylone was rapidly acquired by 87.5% of rats and was maintained across a range of doses, producing an inverted U-shaped dose-response curve. Rank order demand for the individual constituents was MDPV > methylone > caffeine. Demand for the 3:1 (but not 10:1) methylone + caffeine mixture was greater than that for methylone alone, and demand for MDPV alone was similar to both MDPV + caffeine mixtures evaluated.

Conclusions: These studies provide additional evidence that although methylone is an effective reinforcer, combining methylone with caffeine results in an enhanced reinforcing effectiveness compared to methylone alone. Thus, abused "bath salts" preparations containing synthetic cathinones and caffeine may have higher abuse liability than preparations containing only synthetic cathinones.