Adolescent d-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood

Chloe J. Jordan, Carley Lemay, Linda P. Dwoskin, Kathleen M. Kantak

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Rationale: Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adolescents remain controversial with respect to later development of cocaine abuse. Past research demonstrated that adolescent methylphenidate treatment increased several aspects of cocaine self-administration during adulthood using the spontaneously hypertensive rat (SHR) model of ADHD. Presently, we determined effects of the alternate stimulant medication, d-amphetamine, on cocaine self-administration. Objectives: We tested the hypothesis that adolescent d-amphetamine would not increase cocaine self-administration in adult SHR, given that d-amphetamine has a different mechanism of action than methylphenidate. Methods: A pharmacologically relevant dose of d-amphetamine (0.5 mg/kg) or vehicle was administered throughout adolescence to SHR and two control strains, Wistar-Kyoto (WKY) and Wistar (WIS). Three aspects of cocaine abuse vulnerability were assessed in adulthood after discontinuing adolescent treatments: acquisition rate and dose-related responding under fixed (FR) and progressive (PR) ratio schedules. Results: Adult SHR acquired cocaine self-administration faster and self-administered more cocaine across multiple doses compared to WKY and WIS under FR and PR schedules, indicating that SHR is a reliable animal model of comorbid ADHD and cocaine abuse. Relative to vehicle, SHR and WIS with adolescent d-amphetamine treatment self-administered less cocaine upon reaching acquisition criteria, and WIS additionally acquired cocaine self-administration more slowly and had downward shifts in FR and PR cocaine dose-response curves. WKY with adolescent d-amphetamine treatment acquired cocaine self-administration more quickly relative to vehicle. Conclusions: In contrast to methylphenidate, adolescent d-amphetamine did not augment cocaine self-administration in SHR. Adolescent d-amphetamine treatment actually protected against cocaine abuse vulnerability in adult SHR and WIS.

Original languageEnglish
Pages (from-to)3891-3903
Number of pages13
Issue number23-24
StatePublished - Dec 1 2016

Bibliographical note

Funding Information:
National Institutes of Health grant DA011716 and the Clara Mayo Memorial Fellowship at Boston University.

Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.


  • Adolescence
  • Attention deficit/hyperactivity disorder
  • Cocaine self-administration
  • Spontaneously hypertensive rat
  • d-Amphetamine

ASJC Scopus subject areas

  • Pharmacology


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