2012年10月，饶毅实验室在Journal of Neuroscience （《神经科学杂志》）杂志发表题为“性拒绝的分子遗传学分析：鱆胺及其受体OAMB参与果蝇求偶条件化”文章。文中揭示了果蝇脑内鱆胺及其受体OAMB在求偶学习中的作用。
美国Brandeis大学的Siegel和Hall于1979年发现，雌果蝇与雄果蝇交配后拒绝第三者插足。如果一只雄蝇追求已经交配过的雌蝇，而被反复、甚至带有“暴力”地拒绝后，“失恋”的雄蝇对追求雌蝇兴趣下降，不仅不愿追交配过的雌蝇、而且不愿追未交配的“处女蝇”。，这一现象称为“求偶条件化”（courtship conditioning），也称“求偶学习”(courtship learning)。
饶毅实验室的研究生周传等通过应用分子生物学、遗传学、现代生物物理成像等多学科技术，研究了求偶学习的分子机理。他们的研究集中于神经递质鱆胺及其受体OAMB。
他们发现因为基因缺失而不能合成鱆胺的雄蝇，不出现求偶学习，在一再被拒绝以后，继续一如既往地追求雌蝇。通过应用分子遗传操纵，周传等激活含鱆胺的神经元，结果可以抑制雄蝇求偶，并且能代替交配的雌蝇“教训”雄蝇学会减少求偶。这些结果表明鱆胺对于求偶学习是必要而且充分的。他们进一步发现，鱆胺受体OAMB介导鱆胺部分作用，而不是全部作用。OAMB对于求偶学习是必需的，但非充分的。所以，周传等提出还有其他鱆胺受体参加介导鱆胺在求偶学习过程中的作用。
这项研究是多个实验室合作的结果。除了饶毅实验室，还有科学院生物物理所焦仁杰的研究生黄海、美国加州大学王竞实验室的Kim、台湾清华大学江安世实验室的研究生林暄文、美国德州大学的韩实验室等。北京的研究获得科技部和北京市的支持。（生物谷Bioon.com）
doi: 10.1523/JNEUROSCI.0517-12.2012
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Molecular Genetic Analysis of Sexual Rejection: Roles of Octopamine and Its Receptor OAMB in Drosophila Courtship Conditioning
Chuan Zhou , Hai Huang, Susy M. Kim, Hsuanwen Lin, Xianglan Meng, Kyung-An Han, Ann-Shyn Chiang, Jing W. Wang, Renjie Jiao, and Yi Rao
After Drosophila males are rejected by mated females, their subsequent courtship is inhibited even when encountering virgin females. Molecular mechanisms underlying courtship conditioning in the CNS are unclear. In this study, we find that tyramine β hydroxylase (TβH) mutant males unable to synthesize octopamine (OA) showed impaired courtship conditioning, which could be rescued by transgenic TβH expression in the CNS. Inactivation of octopaminergic neurons mimicked the TβH mutant phenotype. Transient activation of octopaminergic neurons in males not only decreased their courtship of virgin females, but also produced courtship conditioning. Single cell analysis revealed projection of octopaminergic neurons to the mushroom bodies. Deletion of the OAMB gene encoding an OA receptor expressed in the mushroom bodies disrupted courtship conditioning. Inactivation of neurons expressing OAMB also eliminated courtship conditioning. OAMB neurons responded robustly to male-specific pheromone cis-vaccenyl acetate in a dose-dependent manner. Our results indicate that OA plays an important role in courtship conditioning through its OAMB receptor expressed in a specific neuronal subset of the mushroom bodies.
