Activation of ventral tegmental area dopamine neurons produces wakefulness through dopamine D2-like receptors in mice
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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/D3 receptor antagonist raclopride, but not by the D1 receptor antagonist SCH23390. These findings indicate that the activation of VTA dopamine neurons promotes wakefulness via D2/D3 receptors.
KeywordsChemogenetics Sleep DAT-Cre mice Midbrain Substantia nigra D1 receptors
Our research was supported by Japan Society for the Promotion of Science Grant 15K18359 (to Y.O.), 26220207/16K18358 (to T.K.), 26640025 (to Y.T.), and 2604762 (to M.L.); a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Grant-in-Aid for Scientific Research on Innovative Areas “Living in Space”, 16H01629, to M.L.); a CREST grant from the Japan Science and Technology Agency (to M.L.); the World Premier International Research Center Initiative (WPI) from MEXT (to Y.O., T.K., Y.T., Y.C., and M.L.); a grant from the Japan Foundation for Applied Enzymology (to Y.O.) and a grant from The Naito Foundation, Japan (to M.L.).
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Conflict of interest
The authors declare no competing financial interests.
- Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky-Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF (2011) Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31(27):10067–10075. doi: 10.1523/JNEUROSCI.6730-10.2011 CrossRefPubMedPubMedCentralGoogle Scholar
- Lena I, Parrot S, Deschaux O, Muffat-Joly S, Sauvinet V, Renaud B, Suaud-Chagny MF, Gottesmann C (2005) Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep–wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats. J Neurosci Res 81(6):891–899. doi: 10.1002/jnr.20602 CrossRefPubMedGoogle Scholar
- Paxinos G, Franklin K (2001) The mouse brain in stereotaxic coordinates. Academic, San DiegoGoogle Scholar
- Wang YQ, Li R, Wang DR, Cherasse Y, Zhang Z, Zhang MQ, Lavielle O, McEown K, Schiffmann SN, de Kerchove d’Exaerde A, Qu WM, Lazarus M, Huang ZL (2016) Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep in rodents. Brain Struct Funct. doi: 10.1007/s00429-016-1281-2 Google Scholar