Marsh Laura E, Terry Robyn, Whittaker Alexandra L, Hiendleder Stefan, Ralph Cameron R
School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy Campus, Roseworthy, SA 5371, Australia.
South Australian Research and Development Institute, Livestock Sciences, Roseworthy Campus, Roseworthy, SA 5371, Australia.
Animals (Basel). 2020 Mar 18;10(3):504. doi: 10.3390/ani10030504.
Animal welfare assessment requires measures for positive affective state. Pharmacological agents that manipulate affective state can be used to evaluate novel biomarkers for affective state assessment. However, to validate that an agent has modified brain function, a reliable indicator is required. Circulating cortisol has been used as a reporter for effective delivery of the antidepressant selective serotonin reuptake inhibitor (SSRI) fluoxetine hydrochloride to the brain in humans and sheep. Here, we tested cortisol as a reporter for effective delivery of fluoxetine hydrochloride to the pig brain. We hypothesized that following administration of SSRI, innervation of the serotonergic reward pathway would result in activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased circulating cortisol levels. Large White-Landrace gilts received either a single intravenous dose of 100 mg fluoxetine hydrochloride suspended in 10 mL saline (n = 4), or 10 mL saline alone (n = 4). Blood samples were collected every 15 min for one hour prior to, and six hours post-treatment. The interaction of treatment x time on mean plasma cortisol levels between 15-165 min post-treatment was significant ( = 0.048) with highest cortisol concentrations of SSRI treated pigs versus controls (+ 98%) at 135 min post-treatment. However, individual cortisol profiles after SSRI treatment revealed high inter-individual variation in response. We conclude that, while combined data imply that plasma cortisol may be a readout for SSRI efficacy, inter-individual variation in SSRI response may preclude application of this approach in the pig. Given the current limited sample size, further research to confirm these findings is needed.
动物福利评估需要对积极情感状态进行测量。可使用能调节情感状态的药物制剂来评估用于情感状态评估的新型生物标志物。然而，为了验证一种制剂是否改变了脑功能，需要一个可靠的指标。循环皮质醇已被用作人类和绵羊中抗抑郁药选择性5-羟色胺再摄取抑制剂（SSRI）盐酸氟西汀有效输送至大脑的报告物。在此，我们测试了皮质醇作为盐酸氟西汀有效输送至猪脑的报告物。我们假设，给予SSRI后，血清素能奖赏通路的神经支配会导致下丘脑-垂体-肾上腺（HPA）轴激活，从而使循环皮质醇水平升高。大白-长白母猪接受单次静脉注射100毫克悬浮于10毫升生理盐水中的盐酸氟西汀（n = 4），或仅接受10毫升生理盐水（n = 4）。在治疗前1小时和治疗后6小时，每隔15分钟采集血样。治疗后15 - 165分钟之间，治疗×时间对平均血浆皮质醇水平的交互作用显著（ = 0.048），在治疗后135分钟时，接受SSRI治疗的猪的皮质醇浓度相对于对照组最高（+ 98%）。然而，SSRI治疗后的个体皮质醇谱显示个体反应存在高度差异。我们得出结论，虽然综合数据表明血浆皮质醇可能是SSRI疗效的一个读数，但SSRI反应的个体差异可能会妨碍该方法在猪身上的应用。鉴于目前样本量有限，需要进一步研究来证实这些发现。
