Instituto de Investigación Médica Mercedes y Martín Ferreyra. INIMEC-CONICET, Córdoba, Argentina.
Physiol Behav. 2011 Sep 1;104(3):398-407. doi: 10.1016/j.physbeh.2011.04.029. Epub 2011 Apr 30.
This study of the participation of the serotonergic system in the inhibitory effect of estrogen on induced sodium appetite in female rats explores sodium appetite induced by Furosemide and low sodium diet treatment (DEP) in normally cycling rats and in ovariectomized rats with and without estradiol replacement (OVX, OVX+E(2)). We also analyzed the neural activity of serotonergic neurons of the dorsal raphe nucleus (DRN) as well as the activity of other brain nuclei previously found to be involved in sodium and water balance in sodium depleted animals without access to the intake test. For this purpose, we examined the brain Fos, Fos-serotonin and Fos-vasopressin immunoreactivity patterns in diestrus (D), estrus (E), OVX and OVX+E(2) rats subjected to DEP. Female rats in E and OVX+E(2) exhibited a significant decrease in induced sodium intake compared with females in D and OVX. This estrogen-dependent inhibition on induced sodium appetite (approximately 50% reduction) can be correlated with changes in Fos activation observed in the organum vasculosum of the lamina terminalis (OVLT) and DRN, in response to sodium depletion. Given our previous observations in males, the expected sodium depletion-induced activity of the OVLT was found to be absent in OVX+E(2) females, while the usual inhibitory tonic activity of serotonergic neurons of the DRN, instead of decreasing after sodium depletion, increases or remains unchanged in OVX+E(2)-DEP and E-DEP females, respectively. Regarding urinary water and sodium excretion 3h after furosemide treatment, E-DEP and OVX+E(2)-DEP animals excreted smaller volumes of more highly concentrated urine than depleted D and OVX rats. Twenty hours after sodium depletion, the same groups of animals also showed a significant increase in the number of Fos-AVP immunoreactive neurons within the supraoptic nucleus, compared with D-DEP. In summary, our results demonstrate an estrogen-dependent inhibition of induced sodium appetite in normally cycling rats and ovariectomized animals with estradiol replacement, which may involve an interaction between excitatory neurons of the OVLT and inhibitory serotonergic cells of the DRN. The main finding is thus serotonergic system involvement as a possible mechanism in the inhibitory action of estrogen on induced sodium appetite.
本研究旨在探讨 5-羟色胺能系统在雌激素抑制雌性大鼠诱导性钠食欲中的作用，研究对象为正常发情周期的雌性大鼠和接受呋塞米及低钠饮食处理（DEP）的去卵巢大鼠（OVX），以及接受去卵巢加雌二醇替代治疗的大鼠（OVX+E2）。我们还分析了背侧中缝核（DRN）的 5-羟色胺能神经元的神经活动，以及在没有摄入测试的情况下参与钠和水平衡的其他脑核的活动。为此，我们在处于动情前期（D）、动情期（E）、OVX 和 OVX+E2 的大鼠中，观察了接受 DEP 处理的大鼠的脑 Fos、Fos-5-羟色胺和 Fos-血管加压素免疫反应模式。与处于 D 和 OVX 状态的雌性大鼠相比，E 和 OVX+E2 状态的雌性大鼠的诱导性钠摄入显著减少。这种雌激素依赖性的对诱导性钠食欲的抑制（约减少 50%）与在 lamina terminalis 的血管器官（OVLT）和 DRN 中观察到的 Fos 激活变化相关，这些变化是对钠耗竭的反应。鉴于我们在雄性大鼠中的先前观察结果，OVLT 的预期钠耗竭诱导活性在 OVX+E2 雌性大鼠中不存在，而 DRN 中的 5-羟色胺能神经元的通常抑制性紧张性活动，在接受 DEP 处理的 OVX+E2 和 E 雌性大鼠中，不是在钠耗竭后减少，而是分别增加或保持不变。关于呋塞米处理后 3 小时的尿钠和尿水量，与接受 DEP 处理的 D 和 OVX 大鼠相比，E-DEP 和 OVX+E2-DEP 动物的尿体积较小，尿液浓缩度更高。在钠耗竭后 20 小时，相同的动物组在视上核中的 Fos-AVP 免疫反应性神经元数量也显著增加，与 D-DEP 相比。总之，我们的结果表明，在正常发情周期的大鼠和接受雌二醇替代治疗的去卵巢大鼠中，雌激素依赖性地抑制了诱导性钠食欲，这可能涉及到 OVLT 的兴奋性神经元和 DRN 的抑制性 5-羟色胺能细胞之间的相互作用。因此，主要发现是 5-羟色胺能系统参与了雌激素对诱导性钠食欲的抑制作用，这可能是一种机制。
