| 研究実績の概要 |
The sleeping habits of humans are unique in the sense that we often defy sleep and stay awake for occupational and recreational reasons or other life-style choices. The motivation to defy sleep and stay awake for a wide range of life-style choices is often accompanied by the use of psychoactive substances, most prominently caffeine, but also prescription drugs such as Modafinil.
We have demonstrated that caffeine induces wakefulness by blocking the action of adenosine on A2A receptors (A2AR) in the nucleus accumbens (NAc; Lazarus M, et al., J. Neurosci. 2011, p. 10067). Adenosine promotes sleep, however the extent to which these A2AR-positive NAc neurons contribute to sleep regulation was previously unknown. Pharmacological activation of A2ARs by the agonist CGS21680 increased non rapid eye movement (NREM) sleep in wild type, but not NAc-specific A2AR KO mice. Optogenetic (channelrhodopsin, ChR2) activation of NAc A2AR neurons induces robust NREM sleep.
Our observations provide the first direct evidence that adenosine and A2AR neurons in the NAc are not only involved in promoting behavioral inactivity (inhibition of movement) but also play a major role in regulating sleep. These findings further suggest the intriguing possibility that the NAc might be a key site through which sleep and wakefulness are regulated by behavioral processes and, by extension, that motivational state may be an important fundamental regulator of sleep and wakefulness (Lazarus M, et al., Trends Neurosci. 2012, p. 723; Lazarus M, et al., Curr. Opin. Neurobiol. 2013, p. 780).
|
