title: Dopamine transporter-related effects of modafinil in rhesus monkeys.
abstract: BACKGROUND
  Modafinil is currently used as a treatment for daytime sleepiness.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd, Atlanta, GA 30329, USA.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.forename: Eileen
authors.initials: E
authors.lastname: Kessler
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Murnane
authors.forename: Jessica C
authors.initials: JC
authors.lastname: McClung
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Howell
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D008253:Macaca mulatta; D008297:Male; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D050483:Dopamine Plasma Membrane Transport Proteins; D000077408:Modafinil
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