Effects of Response‐Contingent and Non‐Contingent Drug History on the Development of High Levels of MDPV Self‐Administration

Abstract

A subset of rats that self‐administer synthetic cathinones, such as 3,4‐methylenedioxypyrovalerone (MDPV), develop high levels of drug intake and compulsive‐like patterns of responding that may be related to the compulsive, binge‐like patterns of cathinone (e.g., “bath salts”) use reported in humans. Once this “high‐responder” phenotype is established, it transfers to other stimulants; however, a prior history of responding for cocaine, but not food, has been shown to prevent or delay the development of this phenotype. These findings suggested that cocaine produces neuroplastic changes that can prevent or delay the transition to high levels of MDPV intake. The present studies aimed to evaluate whether 1) response contingent and non‐contingent cocaine histories are equally effective at preventing high levels of MDPV intake; and 2) response contingent and non‐contingent MDPV histories are sufficient to establish the high‐responder phenotype in rats self‐administering cocaine. Four groups of male Sprague‐Dawley rats were assigned to initially receive MDPV or cocaine in a response contingent or non‐contingent manner using a “yoked” self‐administration paradigm under a fixed ratio (FR) 1 schedule (i.e., response contingent drug infusions delivered to rat A were paired with non‐contingent infusions of the same drug to rat B). After 20 sessions of this yoked MDPV or cocaine self‐administration procedure (10 sessions at FR1, 10 sessions at FR5), all rats were allowed to self‐administer the alternate drug under an FR5 schedule for an additional 20 sessions (e.g. both cocaine groups now self‐administered MDPV). Subsequently, full FR5 dose response curves were generated by dose substitution. These studies found that, unlike response‐contingent cocaine delivery, non‐contingent cocaine is unable to prevent the development of high levels of MDPV self‐administration. Additionally, non‐contingent MDPV is not sufficient to establish high levels of cocaine intake. These results suggest that the contingencies surrounding drug delivery are important for both establishing and preventing the high‐responder phenotype, indicating that both a behavioral and pharmacological history may be important for the transition from regulated to compulsive patterns of drug intake.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 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.