MDPV Self‐Administration in Female Rats: Influence of Reinforcement History

Abstract

Synthetic cathinones are designer stimulants found in “bath salts” preparations and are associated with high rates of abuse and toxicity. One of the most widely available and abused cathinones, 3,4‐methylenedioxypyrovalerone (MDPV), has been shown to be an effective reinforcer in male rats, but its abuse‐related effects have not been studied in female rats. Previous research found that a subset of male rats trained to self‐administer MDPV developed high levels of drug intake (“high‐responders”), earning ~3‐times as much MDPV as the remaining rats (“low‐responders”). However, the mechanism(s) underlying this transition to high levels of drug intake in a subset of rats self‐administering MDPV are unclear. The present study aimed to: 1) evaluate whether female rats would also engage in high levels of MDPV intake; and 2) explore the influence of reinforcement history on the development of this high‐responder phenotype. To explore these issues, three groups of female Sprague Dawley rats were initially trained to respond for either MDPV (0.032 mg/kg/inf), cocaine (0.32 mg/kg/inf), or food (45‐mg grain pellet) under a fixed ratio 1 schedule of reinforcement. After 20 days of responding for their initial reinforcer, the cocaine‐ and food‐trained rats responded for MDPV for an additional 20 days. Dose‐response curves for MDPV were generated under fixed ratio 5 and progressive ratio schedules of reinforcement to determine the reinforcing potency and reinforcing effectiveness of MDPV, respectively. These studies found that, similar to male rats, a subset of MDPV‐trained female rats developed high levels of MDPV intake. In contrast, none of the cocaine‐ or food‐trained female rats exhibited high levels of responding for their respective reinforcers (cocaine or food); however, after responding for MDPV, a subset of food‐trained rats also developed high levels of MDPV intake. Cocaine‐trained rats never exhibited high levels of responding, regardless of whether cocaine or MDPV was available. The MDPV‐ and food‐trained high‐responders engaged in higher levels of intake across a range of doses under fixed ratio, but not progressive ratio, schedules of reinforcement, suggesting that differences in MDPV intake were not related to differences in the reinforcing potency or effectiveness of MDPV between the high‐ and low‐responding rats. Although these studies suggest that different reinforcement histories can facilitate (e.g., MDPV or food) or prevent (e.g., cocaine) the transition to high levels of MDPV intake, the pharmacological, behavioral, neurobiological, and/or genetic determinants of the high‐responder phenotype are currently unclear. Future studies will continue to explore the factors that contribute to the high levels of MDPV intake as they may be important for understanding individual differences in and/or binge patterns of drug‐taking behavior in humans.Support or Funding InformationThis work was supported by NIH/NIDA grant (R01 DA039146; GTC), NIDA‐ and NIAAA‐IRPs (KCR), and NIH Predoctoral Training Program in the Neurosciences (T32 NS082145; MRD).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.