Neckameyer W S
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63108, USA.
Dev Biol. 1996 Jun 15;176(2):209-19. doi: 10.1006/dbio.1996.0128.
Manipulation of dopamine levels by inhibition of tyrosine hydroxylase activity was accomplished in Drosophila melanogaster larval instars by feeding enzyme inhibitors for a 24-hr period. Behavioral assays performed immediately after treatment demonstrated that larval phototaxis, salt aversion, and heptanol preference were unaffected by reduced levels of dopamine. Within a few hours of treatment, the larvae ceased exploratory behavior and were unresponsive to external stimuli; these larvae eventually died. This behavior is strikingly similar to that displayed by dopamine-deficient transgenic mice. Treated larvae placed immediately onto normal food (to replenish dopamine levels) showed significant developmental delays and decreased fertility as adults. The lethality, developmental retardation, and decrease in fertility were reversed by addition of L-DOPA to inhibitor-containing food, suggesting that these effects were due solely to inhibition of tyrosine hydroxylation. Depletion of dopamine in newly eclosed females resulted in abnormally developed ovaries. These results suggest that the enzymatic function of tyrosine hydroxylase is vital and that reduced levels of dopamine result in akinesia and lethality, developmental retardation, and decreased fertility.
通过在24小时内喂食酶抑制剂，在黑腹果蝇幼虫龄期实现了通过抑制酪氨酸羟化酶活性来操纵多巴胺水平。处理后立即进行的行为分析表明，幼虫的趋光性、厌盐性和庚醇偏好不受多巴胺水平降低的影响。在处理后的几个小时内，幼虫停止了探索行为，对外界刺激无反应；这些幼虫最终死亡。这种行为与多巴胺缺乏的转基因小鼠表现出的行为惊人地相似。立即将处理过的幼虫置于正常食物上（以补充多巴胺水平），成年后显示出明显的发育延迟和生育力下降。通过在含抑制剂的食物中添加左旋多巴，可逆转致死率、发育迟缓以及生育力下降，这表明这些影响完全是由于酪氨酸羟化受到抑制所致。新羽化雌性果蝇体内多巴胺的耗竭导致卵巢发育异常。这些结果表明，酪氨酸羟化酶的酶功能至关重要，多巴胺水平降低会导致运动不能和致死率、发育迟缓以及生育力下降。
