Dopamine transporter-related effects of modafinil in rhesus monkeys

Show simple item record Andersen, Monica L. [UNIFESP] Kessler, Eileen Murnane, Kevin S. McClung, Jessica C. Tufik, Sergio [UNIFESP] Howell, Leonard L. 2016-01-24T13:59:44Z 2016-01-24T13:59:44Z 2010-06-01
dc.identifier.citation Psychopharmacology. New York: Springer, v. 210, n. 3, p. 439-448, 2010.
dc.identifier.issn 0033-3158
dc.description.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. en
dc.description.sponsorship USPHS
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 439-448
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartof Psychopharmacology
dc.rights Acesso restrito
dc.subject Modafinil en
dc.subject Cocaine en
dc.subject Reinstatement en
dc.subject Nonhuman primate en
dc.subject PET en
dc.subject In vivo microdialysis en
dc.subject Dopamine en
dc.subject Imaging en
dc.subject Sleep en
dc.title Dopamine transporter-related effects of modafinil in rhesus monkeys en
dc.type Artigo
dc.contributor.institution Emory Univ
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
dc.description.affiliation Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, Brazil
dc.description.affiliation Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, Brazil
dc.description.sponsorshipID USPHS: DA10344
dc.description.sponsorshipID USPHS: DA00517
dc.description.sponsorshipID USPHS: RR00165
dc.description.sponsorshipID FAPESP: 98/14303
dc.identifier.doi 10.1007/s00213-010-1839-2
dc.description.source Web of Science
dc.identifier.wos WOS:000277941000013


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