Vázquez D M, López J F, Van Hoers H, Watson S J, Levine S
Endocrine Division, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
Brain Res. 2000 Feb 7;855(1):76-82. doi: 10.1016/s0006-8993(99)02307-0.
Several studies have demonstrated that 5-HT1A and 5-HT2A receptors are altered in rat brain following chronic stress. While this is true in the adult animal, this may be different in the developing animal, which has a limited corticosterone response to acute challenges between days 3 and 14 of life.
We investigated the effect of maternal deprivation on 5-HT2A and 5-HT1A receptor mRNA levels in the developing brain. In situ hybridization was used to quantify gene expression in rat pups at three ages: 6, 9, and 12 days old. In each age group, half were maternally deprived for 24 h and half were kept with their mothers. Maternally deprived animals showed elevated ACTH and corticosterone plasma levels when compared to NDEP animals, significantly elevated 5-HT1A mRNA levels in the CA1 hippocampal region and, significantly elevated 5-HT2A mRNA levels in the parietal cortex. No changes were observed in 5-HT1A or 5-HT-transporter mRNA levels in the dorsal raphe. Our results indicate that post-synaptic 5-HT receptors in the developing hippocampus and cortex are sensitive to maternal deprivation. Because hippocampal 5-HT1A gene expressions are known to decrease in the adult animal after chronic glucocorticoid elevation, this data also suggests that other mechanisms, perhaps central, predominate during development.
多项研究表明，慢性应激后大鼠脑中的5-HT1A和5-HT2A受体发生改变。虽然在成年动物中确实如此，但在发育中的动物中可能有所不同，发育中的动物在出生后第3天至第14天对急性挑战的皮质酮反应有限。
我们研究了母体剥夺对发育中大脑中5-HT2A和5-HT1A受体mRNA水平的影响。采用原位杂交技术对3个年龄段（6日龄、9日龄和12日龄）的大鼠幼崽的基因表达进行定量分析。在每个年龄组中，一半幼崽被母体剥夺24小时，另一半与母亲在一起。与未被母体剥夺的动物相比，被母体剥夺的动物血浆促肾上腺皮质激素（ACTH）和皮质酮水平升高，海马CA1区5-HT1A mRNA水平显著升高，顶叶皮质5-HT2A mRNA水平显著升高。在中缝背核中未观察到5-HT1A或5-羟色胺转运体mRNA水平的变化。我们的结果表明，发育中的海马体和皮质中的突触后5-羟色胺受体对母体剥夺敏感。由于已知成年动物在慢性糖皮质激素升高后海马5-HT1A基因表达会降低，该数据还表明在发育过程中可能有其他机制（也许是中枢机制）起主导作用。
