Dopamine transporter-related effects of modafinil in rhesus monkeys

Dopamine transporter-related effects of modafinil in rhesus monkeys

Author Andersen, Monica L. Autor UNIFESP Google Scholar
Kessler, Eileen Google Scholar
Murnane, Kevin S. Google Scholar
McClung, Jessica C. Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Howell, Leonard L. Google Scholar
Institution Emory Univ
Universidade Federal de São Paulo (UNIFESP)
Abstract Modafinil is currently used as a treatment for daytime sleepiness.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).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).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).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
Language English
Sponsor USPHS
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number USPHS: DA10344
USPHS: DA00517
USPHS: RR00165
FAPESP: 98/14303
Date 2010-06-01
Published in Psychopharmacology. New York: Springer, v. 210, n. 3, p. 439-448, 2010.
ISSN 0033-3158 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 439-448
Origin http://dx.doi.org/10.1007/s00213-010-1839-2
Access rights Closed access
Type Article
Web of Science ID WOS:000277941000013
URI http://repositorio.unifesp.br/handle/11600/32576

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