Dopamine transporter-related effects of modafinil in rhesus monkeys

dc.contributor.authorAndersen, Monica L. [UNIFESP]
dc.contributor.authorKessler, Eileen
dc.contributor.authorMurnane, Kevin S.
dc.contributor.authorMcClung, Jessica C.
dc.contributor.authorTufik, Sergio [UNIFESP]
dc.contributor.authorHowell, Leonard L.
dc.contributor.institutionEmory Univ
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:59:44Z
dc.date.available2016-01-24T13:59:44Z
dc.date.issued2010-06-01
dc.description.abstractModafinil 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.en
dc.description.affiliationEmory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, Brazil
dc.description.affiliationEmory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipUSPHS
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDUSPHS: DA10344
dc.description.sponsorshipIDUSPHS: DA00517
dc.description.sponsorshipIDUSPHS: RR00165
dc.description.sponsorshipIDFAPESP: 98/14303
dc.format.extent439-448
dc.identifierhttp://dx.doi.org/10.1007/s00213-010-1839-2
dc.identifier.citationPsychopharmacology. New York: Springer, v. 210, n. 3, p. 439-448, 2010.
dc.identifier.doi10.1007/s00213-010-1839-2
dc.identifier.issn0033-3158
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32576
dc.identifier.wosWOS:000277941000013
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofPsychopharmacology
dc.rightsAcesso restrito
dc.rights.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dc.subjectModafinilen
dc.subjectCocaineen
dc.subjectReinstatementen
dc.subjectNonhuman primateen
dc.subjectPETen
dc.subjectIn vivo microdialysisen
dc.subjectDopamineen
dc.subjectImagingen
dc.subjectSleepen
dc.titleDopamine transporter-related effects of modafinil in rhesus monkeysen
dc.typeArtigo
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