Psychopharmacology

, Volume 210, Issue 3, pp 439–448

Dopamine transporter-related effects of modafinil in rhesus monkeys

  • Monica L. Andersen
  • Eileen Kessler
  • Kevin S. Murnane
  • Jessica C. McClung
  • Sergio Tufik
  • Leonard L. Howell
Original Investigation

Abstract

Rationale

Modafinil is currently used as a treatment for daytime sleepiness.

Objectives

The objectives of this study were to explore the dopamine transporter (DAT)-related effects of modafinil on behavior and in vivo neurochemistry in rhesus monkeys (Macaca mulatta).

Methods

The effects of modafinil (3.0–10 mg/kg, i.v.) were evaluated on locomotor activity, reinstatement of cocaine-maintained behavior, extracellular dopamine levels in the caudate nucleus, and DAT occupancy in the dorsal striatum. Eight subjects were fitted with a collar-mounted activity monitor to evaluate sleep-activity cycles, with 4 days of baseline recording preceding an injection of saline or modafinil (3.0–10 mg/kg). The effects of modafinil (3.0–10 mg/kg) and cocaine (0.3 mg/kg) on reinstatement of behavior that was previously maintained under a second-order schedule of i.v. cocaine delivery were tested in a separate group of subjects (n = 6). Finally, the effects of modafinil (3.0–10 mg/kg) on extracellular dopamine levels and DAT occupancy in vivo were characterized using microdialysis and positron emission tomography, respectively, in a within-subjects design (n = 4).

Results

Modafinil significantly increased nighttime locomotor activity and reinstated cocaine-maintained behavior but did not affect daytime locomotor activity. Modafinil significantly increased striatal extracellular dopamine levels at a dose that resulted in DAT occupancy of 64.4% (putamen) and 60.2% (caudate).

Conclusion

The behavioral and in vivo dopaminergic effects of modafinil are consistent with the profile of a low potency DAT inhibitor and may indicate potential for abuse at high doses.

Keywords

Modafinil Cocaine Reinstatement Nonhuman primate PET In vivo microdialysis Dopamine Imaging Sleep 

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Monica L. Andersen
    • 1
    • 2
  • Eileen Kessler
    • 1
  • Kevin S. Murnane
    • 1
  • Jessica C. McClung
    • 1
  • Sergio Tufik
    • 2
  • Leonard L. Howell
    • 1
    • 3
  1. 1.Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  2. 2.Department of PsychobiologyUniversidade Federal de São Paulo (UNIFESP)São PauloBrazil
  3. 3.Department of Psychiatry and Behavioral SciencesEmory UniversityAtlantaUSA

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