Individual Differences in the Relative Reinforcing Effects of 3,4‐Methylenedioxypyrovalerone (MDPV) Under Fixed and Progressive Ratio Schedules of Reinforcement in Rats

Abstract

The abuse of “designer drugs” such as “bath salts” over the past 10 years has reached epidemic proportions. 3,4‐Methylenedioxypyrovalerone (MDPV), a synthetic cathinone and common “bath salt” constituent, is classified by the US Drug Enforcement Agency as Schedule I. MDPV has a cocaine‐like mechanism of action and the present study aimed to directly compare the reinforcing effects of MDPV and cocaine in male Sprague‐Dawley rats. When available under a fixed ratio (FR) 1 schedule, a rapid acquisition of responding was observed for both MDPV (0.032 mg/kg/inf; n=28 of 32) and cocaine (0.32 mg/kg/inf; n=13 of 16). Upon increasing the response requirement to an FR5, two distinct patterns of responding for MDPV emerged, with 0.032 mg/kg/inf MDPV maintaining relatively low rates (~35 infusions/90 min) in approximately half of the rats and significantly higher rates of responding (~85 infusions/90 min) in the other rats. These differential patterns of responding were observed across a range of doses of MDPV (0.0032–0.1 mg/kg/inf), as well as when cocaine (0.032–1 mg/kg/inf) was substituted for MDPV. Unlike in rats trained to self‐administer MDPV, the pattern of responding in cocaine‐trained rats was much more homogenous, regardless of whether they responded for cocaine, or MDPV. In order to determine if these differences in FR responding for MDPV were due to individual differences in the reinforcing effectiveness of MDPV, dose‐response curves (n=16) for MDPV (0.001–0.32 mg/kg/inf) were generated under a progressive ratio (PR) schedule, and compared to those obtained for cocaine (0.032–1.78 mg/kg/inf), methamphetamine (0.01–0.178 mg/kg/inf), and caffeine (0.032–1.78 mg/kg/inf). MPDV was the most potent (MDPV > methamphetamine > cocaine >> caffeine) and effective (MDPV > methamphetamine = cocaine >> caffeine) reinforcer. Although the potency of these drugs to maintain PR responding did not differ between the two sub‐sets of rats, those that self‐administered more MDPV under the FR5 schedule also earned significantly more infusions when MDPV was available under a PR schedule. Moreover, these differences were also apparent when methamphetamine, cocaine, and to a lesser degree, caffeine were available for responding under the PR schedule. Although the factors that contributed to unusually high rates of MDPV‐maintained responding, observed in a sub‐set of rats, are unclear, they might be related to individual differences in human drug‐taking behavior.Support or Funding InformationThis study was supported by an NIH research grant (R01 DA039146) from NIDA, as well as the NIH Intramural Research Programs of NIDA and NIAAA.