Influence of Contingent and Noncontingent Drug Histories on the Development of High Levels of MDPV Self-Administration.

ABSTRACT

A subset of rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) develop unusually high levels of drug taking. A history of responding maintained by cocaine, but not food, prevents the development of this high-responder phenotype; however, it is unclear how histories of noncontingent cocaine exposure or self-administering drugs from other pharmacological classes would affect its development. In the current studies, 5 groups of male Sprague-Dawley rats were used to determine whether histories of responding maintained by drugs from different pharmacological classes (e.g., MDPV, cocaine, fentanyl, nicotine, or ketamine) would differentially impact the development of the high-responder phenotype when MDPV was available for self-administration. Two additional groups were used to determine whether noncontingent exposure to cocaine would prevent the development of the high-responder phenotype when MDPV was available for self-administration, and whether noncontingent exposure to MDPV would facilitate the development of the high-responder phenotype when cocaine was available for self-administration. Consistent with previous reports, a history of response-contingent cocaine, and to a lesser extent noncontingent cocaine, prevented the MDPV high-responder phenotype; however, when responding was initially maintained by fentanyl, nicotine, or ketamine, the MDPV high-responder phenotype developed in ∼45% of rats. By manipulating behavioral and pharmacological histories prior to evaluating MDPV self-administration, the current studies provide additional evidence that a history of response-contingent (or noncontingent) cocaine can prevent the transition from well regulated to aberrant drug-taking when responding is maintained by MDPV. Although the mechanism(s) that underlies this novel high-responder phenotype are unknown, elucidation may provide insight into individual differences relating to substance use disorder. SIGNIFICANCE STATEMENT A subset of outbred Sprague-Dawley rats self-administer high levels of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Understanding the behavioral and/or pharmacological factors that can prevent the development of dysregulated MDPV self-administration may provide insight into individual differences in vulnerability to develop a substance use disorder.