Drosophila D1 dopamine receptor mediates caffeine-induced arousal

被引:79
作者
Andretic, Rozi [1 ,3 ]
Kim, Young-Cho [2 ]
Jones, Frederick S. [1 ]
Han, Kyung-An [2 ]
Greenspan, Ralph J. [1 ]
机构
[1] Inst Neurosci, San Diego, CA 92121 USA
[2] Penn State Univ, Dept Biol, University Pk, PA 16802 USA
[3] Univ Rijeka, Dept Psychol, Rijeka 51000, Croatia
基金
美国国家科学基金会;
关键词
mutants; sleep; adenosinergic; methamphetamine; mushroom bodies;
D O I
10.1073/pnas.0806776105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The arousing and motor-activating effects of psychostimulants are mediated by multiple systems. In Drosophila, dopaminergic transmission is involved in mediating the arousing effects of methamphetamine, although the neuronal mechanisms of caffeine (CAFF)induced wakefulness remain unexplored. Here, we show that in Drosophila, as in mammals, the wake-promoting effect of CAFF involves both the adenosinergic and dopaminergic systems. By measuring behavioral responses in mutant and transgenic flies exposed to different drug-feeding regimens, we show that CAFFinduced wakefulness requires the Drosophila D1 dopamine receptor (dDA1) in the mushroom bodies. In WT flies, CAFF exposure leads to downregulation of dDA1 expression, whereas the transgenic overexpression of dDA1 leads to CAFF resistance. The wake-promoting effects of methamphetamine require a functional dopamine transporter as well as the dDA1, and they engage brain areas in addition to the mushroom bodies.
引用
收藏
页码:20392 / 20397
页数:6
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