Comparison of the Antidepressant-Like Effects of Estradiol and That of Selective Serotonin Reuptake Inhibitors in Middle-Aged Ovariectomized Rats.
Comparison of the Antidepressant-Like Effects of Estradiol and That of Selective Serotonin Reuptake Inhibitors in Middle-Aged Ovariectomized Rats.
复制标题
DOI：
10.3389/fnagi.2016.00311
复制
发表时间：
2016
影响因子：
4.8
通讯作者：
Frazer A
中科院分区：
文献类型：
--
作者：
Benmansour S;Arroyo LD;Frazer A
本研究探讨了年龄和卵巢切除术后（OVX）时间间隔对雌二醇（E2）和选择性血清素再摄取抑制剂（SSRIs）在中年（10个月）OVX大鼠（10m-OVX）抗抑郁（AD）样作用的影响。将这些治疗对10m-OVX的急性或慢性影响与(1)年轻成年（4个月）OVX大鼠（4m-OVX）或老年（14个月）OVX大鼠（14m-OVX）进行比较，时间较短：OVX后2周（+2w）；(2)时间较长：OVX后4或8个月（+4m或+8m）。在海马CA3区的体内计时电流测量中，20 pmol的E2，先前显示在4m-OVX中抑制血清素转运体（SERT），在10m-OVX+2w中没有影响。较高剂量的E2 （40 pmol）增加了T80值（血清素或5-羟色胺（5-HT）清除率的测量值），并阻断了氟伏沙明增加T80的能力。相比之下，雌二醇对10m-OVX+4m的SERT功能没有影响，即使在高于40pmol的剂量下。氟伏沙明在ovx后+2w、+4m和+8m减慢10m-OVX的5-HT清除率，与4m- ovx一样。通过强迫游泳试验，E2 （5 μg/天）治疗2周，先前显示在4m-OVX中诱导ad样效应，在10m-OVX+2w中没有效果。然而，高剂量（10 μg/天）E2诱导ad样效应，显著增加游泳行为和减少静止不动。这种效应在10m-OVX+4m中未见。相比之下，在14m-OVX+2w中获得了显著的AD样效应，从而表明E2缺乏AD效应是由于4个月的激素停用，而不是年龄效应。用SSRI舍曲林治疗2周后，在ovx后+2w， +4m或+8m测试的10m-OVX中获得与4m- ovx相似的ad样效应。因此，雌二醇产生与抑制SERT一致的效果的效力不仅在老年大鼠中下降，而且随着激素消耗时间的延长，其效果也明显减弱。相比之下，SSRIs抑制SERT的能力不受年龄或激素消耗时间长短的影响。
This study investigated the effect of age and that of the post-ovariectomy (OVX) time interval on the antidepressant (AD)-like effects of estradiol (E2) and selective serotonin reuptake inhibitors (SSRIs) in middle-aged (10 month) OVX rats (10m-OVX). Acute or chronic effects of these treatments in 10m-OVX were compared with those (1) in young adult (4-month) OVX rats (4m-OVX) or with older (14-month) OVX rats (14m-OVX), at a short time: 2 weeks post-OVX (+2w) and (2) in 10m-OVX rats after a longer times: 4 or 8 months post-OVX (+4m or +8m). Using in vivo chronoamperometry in the CA3 region of the hippocampus, E2 at 20 pmol, a dose shown previously to inhibit the serotonin transporter (SERT) in 4m-OVX, had no effect in 10m-OVX+2w. A higher dose of E2 (40 pmol) increased T80 value, a measure of serotonin or 5-hydroxytryptamine (5-HT) clearance, and also blocked the ability of fluvoxamine to increase T80. By contrast, estradiol had no effects on SERT function in 10m-OVX+4m, even at a higher dose than 40 pmol. Fluvoxamine slowed 5-HT clearance in 10m-OVX at +2w, +4m and +8m post-OVX as it did in the 4m-OVX. Using the forced swim test, 2 weeks treatment with E2 (5 μg/day), a dose shown previously to induce AD-like effects in 4m-OVX, had no effect in 10m-OVX+2w. However, a higher dose (10 μg/day) of E2 induced an AD-like effect as demonstrated by significantly increased swimming behavior and decreased immobility. This effect was not seen in 10m-OVX+4m. By contrast, significant AD-like effects were obtained in 14m-OVX+2w, thereby demonstrating that the lack of an AD effect of E2 is due to the 4-month hormone withdrawal and not to an age effect. After 2 weeks treatment with the SSRI sertraline, similar AD-like effects were obtained in 10m-OVX tested at +2w, +4m or +8m post-OVX as those found in 4m-OVX. Thus, the potency of estradiol to produce effects consistent with inhibition of the SERT was not only decreased in older rats but its effects were markedly diminished the longer hormonal depletion occurred. By contrast, the ability of SSRIs to inhibit the SERT was not affected either by age or the length of hormonal depletion.