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Sexually dimorphic responses of rats to fluoxetine in the forced swimming test are unrelated to the function of the serotonin transporter in the brain.
SYNAPSE ( IF 2.3 ) Pub Date : 2019-09-09 , DOI: 10.1002/syn.22130
Karolina Domingues 1, 2 , Fernanda Barbosa Lima 1, 2 , Aurea Elizabeth Linder 2 , Fernando Falkenburger Melleu 1 , Anicleto Poli 2 , Inaê Spezia 1 , Patrick Remus Suman 1, 2 , Laís Cristina Theindl 1 , Cilene Lino de Oliveira 1, 2
Affiliation  

Due to the prevalence of depression in women, female rats may be a better models for antidepressant research than males. In male rats, fluoxetine inhibited the serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) which is reducing the immobility time in the repeated forced swimming test (rFST). The performance of female rats in this test is unknown. In this study, responses of male and female rats in the rFST under chronic treatment with fluoxetine and the function of SERT in their brains were examined. Wistar rats received oral fluoxetine (females: 0, 1, 2.5, or 5 mg kg-1 day-1 ; males: 0 or 2.5 mg kg-1 day-1 ; in sucrose 10%, 1.5 ml/rat) 1 hr before the test daily for 12 days over the course of the rFST. rFST consisted of a 15 min pretest followed by 5 min sessions of swimming at 1 (test), 7 (retest 1), and 14 (retest 2) days later. SERT functioning was assessed by ex vivo assays of the frontal cortex and hippocampus of rats. Fluoxetine reduced immobility time of males in the rFST while it failed to do so in females. In vitro treatment with fluoxetine inhibited the uptake of 5-HT of both sexes similarly, while in vivo chronic administration of fluoxetine failed to do so. In summary, rats responded to the chronic treatment with fluoxetine in a sexually dimorphic fashion during the rFST despite the functioning of SERT in their brains remaining equally unchanged. Hence, our data suggest that sexually dimorphic responses to fluoxetine in rFST may be unrelated to the function of SERT in rat brains.

中文翻译:

在强迫游泳试验中,大鼠对氟西汀的两性性反应与血清素转运蛋白在大脑中的功能无关。

由于女性中抑郁症的流行,雌性大鼠可能比雄性大鼠更好地进行抗抑郁研究。在雄性大鼠中,氟西汀抑制5-羟色胺(5-羟色胺,5-HT)转运蛋白(SERT),从而减少了反复强迫游泳试验(rFST)中的固定时间。雌性大鼠在该测试中的表现未知。在这项研究中,雄性和雌性大鼠在长期接受氟西汀治疗的rFST中的反应以及大脑中SERT的功能均得到了研究。Wistar大鼠在1小时前接受口服氟西汀(雌性:0、1、2.5或5 mg kg-1 day-1;雄性:0或2.5 mg kg-1 day-1;蔗糖10%,1.5 ml /大鼠)在rFST的过程中,每天进行12天的测试。rFST包括15分钟的预测试,然后在1天(测试),7天(重新测试1)和14天(重新测试2)之后游泳5分钟。通过离体测定大鼠额叶皮质和海马体来评估SERT功能。氟西汀减少了rFST中男性的不动时间,而女性则没有。氟西汀的体外治疗类似地抑制了男女双方对5-HT的摄取,而氟西汀的体内慢性给药未能做到这一点。总之,尽管在大脑中SERT的功能保持不变,但大鼠在rFST期间以性二态性对氟西汀的慢性治疗有反应。因此,我们的数据表明,rFST中对氟西汀的性双态反应可能与大鼠大脑中SERT的功能无关。氟西汀的体外治疗类似地抑制了男女双方对5-HT的摄取,而氟西汀的体内慢性给药未能做到这一点。总之,尽管SERT在大脑中的功能保持不变,但在rFST期间,大鼠对氟西汀的慢性治疗以性二态性反应。因此,我们的数据表明,rFST中对氟西汀的性双态反应可能与大鼠大脑中SERT的功能无关。氟西汀的体外治疗类似地抑制了男女双方对5-HT的摄取,而氟西汀的体内慢性给药未能做到这一点。总之,尽管SERT在大脑中的功能保持不变,但在rFST期间,大鼠对氟西汀的慢性治疗以性二态性反应。因此,我们的数据表明,rFST中对氟西汀的性双态反应可能与大鼠大脑中SERT的功能无关。
更新日期:2019-11-01
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