Cone Neurological Research Laboratory, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Brain Res. 2010 Jan 15;1310:162-71. doi: 10.1016/j.brainres.2009.11.006. Epub 2009 Nov 11.
The olfactory bulbectomized (OBX) rat is an animal model of depression with neurochemical, neuroendocrinological and behavioral features resembling some human depression. d-Fenfluramine is a 5-HT releasing drug, frequently used in the study of the responsivity of the 5-HT system in subjects with psychiatric disorders, including depression. The aim of the study is to assess the influence of the serotonin-releaser, d-fenfluramine, in the OBX rat model of depression, as measured by the change in the regional cerebral glucose utilization rCGU) following d-fenfluramine injection. Male Sprague-Dawley rats (160-180 g) were used. The rats were divided into OBX and Sham groups. Two weeks following the olfactory bulbectomy or the sham surgery, six rats (randomly assigned) from each group received an i.p. injection of d-fenfluramine with a dose of 5 mg/kg or the same volume of saline. Twenty minutes later, the rCGU rates were measured using 2-[(14)C]deoxyglucose autoradiography. The general linear model statistical analysis has shown that the rCGU in the sham-operated rats treated with d-fenfluramine, compared to the sham-operated rats treated with saline, was lower in 14 (36%) out of 39 examined brain regions. There was no significant difference in the rCGU between the OBX rats treated with d-fenfluramine and OBX rats treated with saline. The results suggest the blunted capacity of the 5-HT system in OBX rats to respond to the challenge by the 5-HT releasing compound, d-fenfluramine. This resembles similar findings in clinical studies on depressed patients.
嗅球切除术（OBX）大鼠是一种具有神经化学、神经内分泌和行为特征类似于人类某些抑郁症的抑郁动物模型。地芬氟拉明是一种 5-HT 释放药物，常用于研究包括抑郁症在内的精神障碍患者 5-HT 系统的反应性。本研究旨在评估 5-HT 释放剂地芬氟拉明对 OBX 大鼠抑郁模型的影响，方法是测量地芬氟拉明注射后局部脑葡萄糖利用率（rCGU）的变化。雄性 Sprague-Dawley 大鼠（160-180g）用于本研究。大鼠分为 OBX 和假手术组。嗅球切除或假手术后两周，每组随机分配 6 只大鼠（n=6）分别接受 5mg/kg 地芬氟拉明或相同体积的生理盐水腹腔注射。20 分钟后，通过 2-[[14C]脱氧葡萄糖]放射性自显影术测量 rCGU 率。一般线性模型统计分析表明，与生理盐水处理的假手术大鼠相比，地芬氟拉明处理的假手术大鼠的 rCGU 在 39 个检查脑区中的 14 个（36%）降低。地芬氟拉明处理的 OBX 大鼠和生理盐水处理的 OBX 大鼠之间的 rCGU 无显著差异。结果表明，OBX 大鼠 5-HT 系统对 5-HT 释放化合物地芬氟拉明的反应能力减弱。这与临床抑郁症患者的类似研究结果相似。
