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.