Green Amanda D, Barr Alasdair M, Galea Liisa A M
Department of Psychology, Neuroscience Program and Brain Research Centre, The University of British Columbia, Vancouver, Canada.
Physiol Behav. 2009 May 25;97(2):259-65. doi: 10.1016/j.physbeh.2009.02.020. Epub 2009 Feb 28.
Previously, a hormone-simulated pregnancy (HSP), and the subsequent 'postpartum' withdrawal in estradiol has been shown to precipitate depressive-like behaviours in the forced swim test in female rats. In this study, we used the HSP and 'postpartum' withdrawal to investigate the impact on sucrose consumption, a model of anhedonia. Rats were assigned to "postpartum", "postpartum"+EB (estradiol benzoate), "postpartum"+IMI (imipramine; a tricyclic antidepressant), "postpartum"+DPN (diarylpropionitrile; an ERbeta agonist), or ovariectomized (OVX) controls and OVX+IMI treatments. All "postpartum" groups received daily hormone injections (estradiol and progesterone) over 23 days to simulate pregnancy, while IMI groups also received daily injections of imipramine. After Day 23, "postpartum" rats were withdrawn from the hormone regimen (mimicking the postpartum decrease in gonadal hormones), and then received daily injections of compounds indicated (DPN, EB, IMI). Rats were tested for consumption of, and preference for, sucrose weekly at baseline, during 'pregnancy' and on 'Postpartum' Days 2-3. During the 'postpartum' period rats in the "postpartum" group had lower sucrose consumption and preference compared to during late-'pregnancy', but no decrease in 'postpartum' consumption or preference was seen in any other groups except "postpartum"+IMI and a decrease in sucrose preference only in the postpartum+EB group from mid-'pregnancy' to 'postpartum'. The OVX +IMI group had decreased sucrose consumption relative to OVX controls, suggesting a negative effect of imipramine on sucrose consumption. Together, these results suggest an important, though complex, role for gonadal hormones in the behavioral changes accompanying this model of depression.
此前,激素模拟妊娠(HSP)以及随后雌二醇的“产后”撤药已被证明会在雌性大鼠的强迫游泳试验中引发类似抑郁的行为。在本研究中,我们利用HSP和“产后”撤药来研究对蔗糖消耗的影响,蔗糖消耗是快感缺失的一种模型。将大鼠分为“产后”组、“产后”+EB(苯甲酸雌二醇)组、“产后”+IMI(丙咪嗪;一种三环类抗抑郁药)组、“产后”+DPN(二芳基丙腈;一种雌激素受体β激动剂)组,或去卵巢(OVX)对照组以及OVX+IMI处理组。所有“产后”组在23天内每天接受激素注射(雌二醇和孕酮)以模拟妊娠,而IMI组还每天接受丙咪嗪注射。在第23天后,“产后”大鼠停止激素给药方案(模拟产后性腺激素的减少),然后每天接受指定化合物(DPN、EB、IMI)的注射。在基线、“妊娠”期间以及“产后”第2 - 3天每周对大鼠进行蔗糖消耗和偏好测试。在“产后”期间,“产后”组大鼠的蔗糖消耗和偏好低于妊娠后期,但除了“产后”+IMI组外,其他组在“产后”期间的消耗或偏好均未降低,并且只有“产后”+EB组从妊娠中期到“产后”蔗糖偏好有所下降。OVX +IMI组相对于OVX对照组蔗糖消耗减少,表明丙咪嗪对蔗糖消耗有负面影响。总之,这些结果表明性腺激素在伴随这种抑郁模型的行为变化中起着重要但复杂的作用。