Slotkin T A, Barnes G A, McCook E C, Seidler F J
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res Dev Brain Res. 1996 May 31;93(1-2):155-61. doi: 10.1016/0165-3806(96)00027-2.
Prenatal stress or exposure to excess glucocorticoids are known to alter central nervous system function and to result in lasting changes in reactions to stress. The potential involvement of specific elements of brainstem serotonergic neurons was examined in the current study. Pregnant rats were given 0.05, 0.2 or 0.8 mg/kg of dexamethasone on gestational days 17, 18 and 19, and the effects on development of the serotonin presynaptic transporter were assessed from birth to young adulthood by measurement of [3H]paroxetine binding to membrane preparations. Dexamethasone produced a dose-dependent retardation of body and brainstem growth but evoked a significant elevation of [3H]paroxetine binding that persisted into adulthood. Effects on [3H]paroxetine binding were robust even at the lowest dose, which did not suppress growth, indicating that the programming of this transporter is more sensitive to glucocorticoids than is general development. At the highest dose, promotional effects on serotonin transporter expression were offset by impaired growth, so that the peak effect was seen at the intermediate dose of dexamethasone. There were no comparable effects on serotonin transmitter levels, indicating selectivity toward promotion of transporter expression as distinct from simply increasing the number of serotonergic nerve terminals or all nerve terminal components. As the effect of prenatal dexamethasone treatment on the serotonin transporter is more persistent than those on other monoamine transporters, and is not shared by postnatal treatment or by treatment in adulthood, it likely represents specific programming by glucocorticoids during the prenatal period. Aberrant serotonergic transporter expression may contribute to alterations of synaptic function that ultimately produce the physiological abnormalities seen after prenatal stress or glucocorticoid treatment.
已知产前应激或暴露于过量糖皮质激素会改变中枢神经系统功能，并导致对应激反应的持久变化。在本研究中，对脑干血清素能神经元的特定元素的潜在参与情况进行了检查。在妊娠第17、18和19天，给怀孕大鼠注射0.05、0.2或0.8mg/kg的地塞米松，并通过测量[3H]帕罗西汀与膜制剂的结合，评估从出生到成年期对血清素突触前转运体发育的影响。地塞米松导致身体和脑干生长呈剂量依赖性迟缓，但引起[3H]帕罗西汀结合显著升高，这种升高持续到成年期。即使在不抑制生长的最低剂量下，对地塞米松结合的影响也很显著，这表明该转运体的编程对糖皮质激素比一般发育更敏感。在最高剂量下，对血清素转运体表达的促进作用被生长受损所抵消，因此在中等剂量的地塞米松下观察到峰值效应。对血清素递质水平没有类似影响，表明对转运体表达促进具有选择性，这与简单增加血清素能神经末梢或所有神经末梢成分的数量不同。由于产前地塞米松治疗对血清素转运体的影响比其他单胺转运体更持久，且产后治疗或成年期治疗不会产生这种影响，它可能代表了产前期间糖皮质激素的特定编程。血清素能转运体表达异常可能导致突触功能改变，最终产生产前应激或糖皮质激素治疗后出现的生理异常。
