Journal of Neural Transmission

, Volume 124, Issue 5, pp 655–667 | Cite as

Chronic oral methylphenidate treatment reversibly increases striatal dopamine transporter and dopamine type 1 receptor binding in rats

  • Lisa S. Robison
  • Mala Ananth
  • Michael Hadjiargyrou
  • David E. Komatsu
  • Panayotis K. Thanos
Psychiatry and Preclinical Psychiatric Studies - Original Article

Abstract

Previously, we created an 8-h limited-access dual bottle drinking paradigm to deliver methylphenidate (MP) to rats at two dosages that result in a pharmacokinetic profile similar to patients treated for attention deficit hyperactivity disorder. Chronic treatment resulted in altered behavior, with some effects persisting beyond treatment. In the current study, adolescent male Sprague–Dawley rats were split into three groups at four weeks of age: control (water), low-dose MP (LD), and high-dose MP (HD). Briefly, 4 mg/kg (low dose; LD) or 30 mg/kg (high dose; HD) MP was consumed during the first hour, and 10 mg/kg (LD) or 60 mg/kg (HD) MP during hours two through eight. Following three months of treatment, half of the rats in each group (n = 8–9/group) were euthanized, and remaining rats went through a 1-month abstinence period, then euthanized. In vitro receptor autoradiography was performed to quantify binding levels of dopamine transporter (DAT), dopamine type 1 (D1R)-like receptors, and dopamine type 2 (D2R)-like receptors using [3H] WIN35,428, [3H] SCH23390, and [3H] Spiperone, respectively. Immediately following treatment, HD MP-treated rats had increased DAT and D1R-like binding in several subregions of the basal ganglia, particularly more caudal portions of the caudate putamen, which correlated with some previously reported behavioral changes. There were no differences between treatment groups in any measure following abstinence. These findings suggest that chronic treatment with a clinically relevant high dose of MP results in reversible changes in dopamine neurochemistry, which may underlie some effects on behavior.

Keywords

Methylphenidate Psychostimulant Dopamine Transporter Reward deficiency syndrome, reward, addiction 

Notes

Acknowledgements

This work was supported by the New York Research Foundation [Q0942016] and the National Institute of Health [R01HD70888].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  • Lisa S. Robison
    • 1
  • Mala Ananth
    • 2
  • Michael Hadjiargyrou
    • 3
  • David E. Komatsu
    • 4
  • Panayotis K. Thanos
    • 5
  1. 1.Department of PsychologyStony Brook UniversityStony BrookUSA
  2. 2.Department of NeurobiologyStony Brook UniversityStony BrookUSA
  3. 3.Department of Life SciencesNew York Institute of TechnologyOld WestburyUSA
  4. 4.Department of OrthopedicsStony Brook UniversityStony BrookUSA
  5. 5.Behavioral Neuropharmacology and Neuroimaging Laboratory On Addictions, Research Institute On AddictionsUniversity at BuffaloBuffaloUSA

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