Recurring Ethanol Exposure Induces Disinhibited Courtship in <em>Drosophila</em>

Alcohol has a strong causal relationship with sexual arousal and disinhibited sexual behavior in humans; however, the physiological support for this notion is largely lacking and thus a suitable animal model to address this issue is instrumental. We investigated the effect of ethanol on sexual behavior in Drosophila. Wild-type males typically court females but not males; however, upon daily administration of ethanol, they exhibited active intermale courtship, which represents a novel type of behavioral disinhibition. The ethanol-treated males also developed behavioral sensitization, a form of plasticity associated with addiction, since their intermale courtship activity was progressively increased with additional ethanol experience. We identified three components crucial for the ethanol-induced courtship disinhibition: the transcription factor regulating male sex behavior Fruitless, the ABC guanine/tryptophan transporter White and the neuromodulator dopamine. fruitless mutant males normally display conspicuous intermale courtship; however, their courtship activity was not enhanced under ethanol. Likewise, white males showed negligible ethanol-induced intermale courtship, which was not only reinstated but also augmented by transgenic White expression. Moreover, inhibition of dopamine neurotransmission during ethanol exposure dramatically decreased ethanol-induced intermale courtship. Chronic ethanol exposure also affected a male's sexual behavior toward females: it enhanced sexual arousal but reduced sexual performance. These findings provide novel insights into the physiological effects of ethanol on sexual behavior and behavioral plasticity.酒精与人类的性唤起及脱抑制性行为存在明确的因果关联，但目前该结论的生理学依据仍较为匮乏，因此构建合适的动物模型以探究该问题至关重要。本研究以果蝇（Drosophila）为模型，探究了乙醇（ethanol）对其性行为的影响。野生型雄性果蝇通常仅会追求雌性而非雄性，但在每日摄入乙醇后，它们会表现出活跃的雄性间求偶行为，这是一种新型的行为脱抑制现象。经乙醇处理的雄性果蝇还出现了行为敏化现象——这是一种与成瘾相关的神经可塑性表现——因为随着乙醇暴露经验的累积，其雄性间求偶行为会逐渐增强。我们鉴定出了三个对乙醇诱导的求偶脱抑制至关重要的组分：调控雄性性别行为的转录因子 (transcription factor) Fruitless、ABC型鸟嘌呤/色氨酸转运蛋白White以及神经调质多巴胺 (dopamine)。fruitless突变型雄性果蝇原本就会表现出显著的雄性间求偶行为，但在乙醇暴露下其求偶活性并未得到增强。同样，white突变型雄性果蝇几乎不会出现乙醇诱导的雄性间求偶行为，而通过转基因表达White不仅能够恢复该行为，还能使其进一步增强。此外，在乙醇暴露期间抑制多巴胺神经传递，会显著降低乙醇诱导的雄性间求偶行为。长期乙醇暴露还会影响雄性果蝇对雌性的性行为：既会增强性唤起，又会降低交配性能。本研究结果为探究乙醇对性行为及行为可塑性的生理学影响提供了全新的视角。