Selective serotonin 2A receptor antagonism attenuates the effects of amphetamine on arousal and dopamine overflow in non-human primates

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dc.contributor.authorMurnane, Kevin S.
dc.contributor.authorAndersen, Monica L. [UNIFESP]
dc.contributor.authorRice, Kenner C.
dc.contributor.authorHowell, Leonard L.
dc.contributor.institutionYerkes Natl Primate Res Ctr
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionNIDA
dc.contributor.institutionNIAAA
dc.contributor.institutionEmory Univ
dc.date.accessioned2016-01-24T14:34:27Z
dc.date.available2016-01-24T14:34:27Z
dc.date.issued2013-10-01
dc.description.abstractThe objective of the present study was to further elucidate the mechanisms involved in the wake-promoting effects of psychomotor-stimulants. Many previous studies have tightly linked the effects of stimulants to dopamine neurotransmission, and some studies indicate that serotonin 2A receptors modulate these effects. However, the role of dopamine in arousal is controversial, most notably because dopamine neurons do not change firing rates across arousal states. in the present study, we examined the wake-promoting effects of the dopamine-releaser amphetamine using non-invasive telemetric monitoring. These effects were evaluated in rhesus monkeys as a laboratory animal model with high translational relevance for human disorders of sleep and arousal. To evaluate the role of dopamine in the wake-promoting effects of amphetamine, we used in vivo microdialysis targeting the caudate nucleus, as this approach provides clearly interpretable measures of presynaptic dopamine release. This is beneficial in the present context because some of the inconsistencies between previous studies examining the role of dopamine in arousal may be related to differences between postsynaptic dopamine receptors. We found that amphetamine significantly and dose-dependently increased arousal at doses that engendered higher extracellular dopamine levels. Moreover, antagonism of serotonin 2A receptors attenuated the effects of amphetamine on both wakefulness and dopamine overflow. These findings further elucidate the role of dopamine and serotonin 2A receptors in arousal, and they suggest that increased dopamine neurotransmission may be necessary for the wake-promoting effects of amphetamine, and possibly other stimulants.en
dc.description.affiliationYerkes Natl Primate Res Ctr, Div Neuropharmacol & Neurol Dis, Atlanta, GA USA
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, São Paulo, Brazil
dc.description.affiliationNIDA, Chem Biol Res Branch, NIH, Bethesda, MD 20892 USA
dc.description.affiliationNIAAA, NIH, Bethesda, MD USA
dc.description.affiliationEmory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipUSPHS
dc.description.sponsorshipNational Institute on Drug Abuse
dc.description.sponsorshipNational Institute on Alcohol Abuse and Alcoholism
dc.description.sponsorshipIDUSPHS: DA010344
dc.description.sponsorshipIDUSPHS: DA012514
dc.description.sponsorshipIDUSPHS: RR000165
dc.format.extent581-588
dc.identifierhttp://dx.doi.org/10.1111/jsr.12045
dc.identifier.citationJournal of Sleep Research. Hoboken: Wiley-Blackwell, v. 22, n. 5, p. 581-588, 2013.
dc.identifier.doi10.1111/jsr.12045
dc.identifier.issn0962-1105
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36778
dc.identifier.wosWOS:000324335300013
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofJournal of Sleep Research
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subject5-HT2Aen
dc.subjectamphetamineen
dc.subjectarousalen
dc.subjectM100907en
dc.subjectmicrodialysisen
dc.subjectrhesus monkeysen
dc.titleSelective serotonin 2A receptor antagonism attenuates the effects of amphetamine on arousal and dopamine overflow in non-human primatesen
dc.typeinfo:eu-repo/semantics/article
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