Department of Animal Sciences, University of Florida, Gainesville, FL, USA.
Department of Animal Sciences, University of Florida, Gainesville, FL, USA.
Domest Anim Endocrinol. 2019 Oct;69:42-50. doi: 10.1016/j.domaniend.2019.04.007. Epub 2019 May 21.
Peripheral serotonin has been shown to regulate important physiological functions such as energy homeostasis and immunity, particularly in rodent and humans, but its role is poorly understood in livestock species. Herein, we tested the safety and effectiveness of increasing serotonin bioavailability in preweaned dairy calves by oral supplementation of a serotonin precursor (5-hydroxytryptophan, 5-HTP) or a serotonin reuptake inhibitor (fluoxetine, FLX). Bull Holstein calves (21 ± 2 d old; N = 24) were fed milk replacer (8 L/d) supplemented with either saline as control (CON, 8 mL/d, n = 8), FLX (40 mg/d, approx. 0.8 mg/kg; n = 8), or 5-HTP (90 mg/d, approx. 1.8 mg/kg; n = 8) for 10 consecutive days in a complete randomized block design. Heart rate (HR), respiration rate, rectal temperature, and health scores were recorded daily. Hip height and body weight were measured at d 1, 5, and 10 relative to initiation of supplementation. Blood samples were collected once before the supplementation period (d 1), during the 10-d supplementation period (daily), and during a 14-d withdrawal period (d 2, 3, 4, 7, and 14 relative to initiation of withdrawal). Cerebrospinal fluid and muscle tissue were collected from a subset of calves (n = 12) that were euthanized after the 10-d supplementation or 14-d withdrawal period. Whole blood serotonin concentrations increased in 5-HTP calves and decreased in FLX calves compared with CON (P < 0.001), indicating that serotonin bioavailability was increased in both groups. Whole blood serotonin concentrations of 5-HTP and FLX calves returned to CON levels after 7 d of withdrawal. All calves grew and were considered healthy throughout the study. In fact, calves fed 5-HTP had higher average daily gain compared with CON (0.87 vs 0.66 ± 0.12 kg/d, P = 0.05). Calves fed FLX had lower HR (P = 0.02) and greater red blood cells and hemoglobin counts on d 10 of supplementation compared with CON (P < 0.01). After the 14-d withdrawal period, FLX was not detected in circulation of FLX calves, but was still present in the muscle tissue. Our results demonstrate that manipulation of the serotonin pathway by supplementing FLX or 5-HTP is a feasible and safe approach in preweaned dairy calves; however, it takes more than 14 d for FLX to be completely withdrawn from the body.
外周血清素已被证明可调节重要的生理功能，如能量平衡和免疫，特别是在啮齿动物和人类中，但在牲畜物种中，其作用知之甚少。在此，我们通过口服补充血清素前体（5-羟色氨酸，5-HTP）或血清素再摄取抑制剂（氟西汀，FLX）来测试增加初乳牛犊血清素生物利用度的安全性和有效性。公牛荷斯坦犊牛（21 ± 2 天龄；N = 24）饲喂代乳（8 L/d），补充盐水作为对照（CON，8 mL/d，n = 8）、FLX（40 mg/d，约 0.8 mg/kg；n = 8）或 5-HTP（90 mg/d，约 1.8 mg/kg；n = 8），连续 10 天，采用完全随机分组设计。每天记录心率（HR）、呼吸频率、直肠温度和健康评分。相对于补充开始，在第 1、5 和 10 天测量臀部高度和体重。在补充期之前（第 1 天）、10 天补充期（每天）和 14 天停药期（相对于停药开始，第 2、3、4、7 和 14 天）采集一次血液样本。从一组接受 10 天补充或 14 天停药的犊牛（n = 12）中收集脑脊液和肌肉组织。与 CON 相比，5-HTP 犊牛的全血血清素浓度升高，FLX 犊牛的全血血清素浓度降低（P < 0.001），表明两组的血清素生物利用度均增加。5-HTP 和 FLX 犊牛的全血血清素浓度在停药 7 天后恢复到 CON 水平。整个研究过程中所有犊牛均生长正常，被认为健康。事实上，与 CON 相比，喂食 5-HTP 的犊牛的平均日增重更高（0.87 与 0.66 ± 0.12 kg/d，P = 0.05）。与 CON 相比，补充 FLX 的犊牛在第 10 天的 HR 更低（P = 0.02），红细胞和血红蛋白计数更高（P < 0.01）。在 14 天停药期后，FLX 不再存在于 FLX 犊牛的循环中，但仍存在于肌肉组织中。我们的结果表明，通过补充 FLX 或 5-HTP 来调节血清素途径是初乳牛犊可行且安全的方法；然而，FLX 需要超过 14 天才能从体内完全清除。
