Peiffer A, Veilleux S, Barden N
Laboratory of Molecular Psychogenetics, CHUL Research Centre, Ste. Foy, Québec, Canada.
Psychoneuroendocrinology. 1991;16(6):505-15. doi: 10.1016/0306-4530(91)90034-q.
The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females. We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.
研究了丙咪嗪、去甲丙咪嗪、酮色林和锂对参与下丘脑-垂体-肾上腺（HPA）轴调控的大鼠脑区II型糖皮质激素受体（GR）mRNA水平的影响，HPA轴失调与重度抑郁症的病理生理学有关。对II型GR mRNA的Northern印迹分析表明，用去甲丙咪嗪或丙咪嗪治疗雄性大鼠可增加下丘脑和海马体的GR mRNA水平。在雌性大鼠的脑区发现，给予丙咪嗪后GR mRNA上调，而去甲丙咪嗪没有效果。酮色林可增加雄性大鼠海马体中GR mRNA的水平，但对雌性大鼠无效。锂也能够显著增加大鼠脑内GR mRNA水平；这种作用在雌性大鼠中尤为明显。我们得出结论，去甲丙咪嗪、丙咪嗪、酮色林和锂可调节大鼠脑内参与HPA轴调控区域的GR mRNA，并且可能在GR基因水平具有共同的作用机制。研究显示了药物对脑GR mRNA含量调节的性别差异，这可能与某些情感障碍患病率的性别差异有关。
