title: Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D2-like receptors in mice.
abstract: A growing body of evidence suggests that dopamine plays a role in sleep-wake regulation, but the dopamine-producing brain areas that control sleep-wake states are unclear. In this study, we chemogenetically activated dopamine neurons in the ventral midbrain of mice to examine the role of these neurons in sleep-wake regulation. We found that activation of dopamine neurons in the ventral tegmental area (VTA), but not in the substantia nigra, strongly induced wakefulness, although both cell populations expressed the neuronal activity marker c-Fos after chemogenetic stimulation. Analysis of the pattern of behavioral states revealed that VTA activation increased the duration of wakefulness and decreased the number of wakefulness episodes, indicating that wakefulness was consolidated by VTA activation. The increased wakefulness evoked by VTA activation was completely abolished by pretreatment with the dopamine D2/D3receptor antagonist raclopride, but not by the D1receptor antagonist SCH23390. These findings indicate that the activation of VTA dopamine neurons promotes wakefulness via D2/D3receptors.
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan. oishi.yo.fu@u.tsukuba.ac.jp.
authors.forename: Yo
authors.initials: Y
authors.lastname: Oishi
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Yonezawa
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanda
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Takata
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Yoan
authors.initials: Y
authors.lastname: Cherasse
authors.affiliation: International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan. lazarus.michael.ka@u.tsukuba.ac.jp.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0003-3863-4474
authors.initials: M
authors.lastname: Lazarus
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D004569:Electroencephalography; D004576:Electromyography; D005838:Genotype; D018345:Mice, Knockout; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*; D014851:Wakefulness / Q000187:drug effects
chemical_list: C000600618:DRD2 protein, mouse; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; C493594:Drd3 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3
keywords: Chemogenetics; D1 receptors; DAT-Cre mice; Midbrain; Sleep; Substantia nigra