Klimek Violetta, Roberson Gary, Stockmeier Craig A, Ordway Gregory A
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216, USA.
J Psychiatr Res. 2003 Sep-Oct;37(5):387-97. doi: 10.1016/s0022-3956(03)00045-1.
Neurochemical imbalance between noradrenergic and serotonergic systems has been postulated to underlie the pathophysiology of psychiatric illnesses involving mood disorders. The present study was designed to examined the possibility that serotonergic innervation of the locus coeruleus (LC) is abnormal in major depression, by measuring two proteins expressed by serotonergic neurons, but not by noradrenergic neurons, in the region of the LC. The specific binding of [(3)H]paroxetine to serotonin transporter (SERT) and of [(3)H]lazabemide to monoamine oxidase (MAO-B) were measured autoradiographically in tissue sections cut transversely at multiple levels along the rostro-caudal extent of the LC, as well as in the caudal portion of the dorsal raphe nucleus, from psychiatrically normal subjects and age-matched subjects with major depression. Under the conditions of the assays, [(3)H]paroxetine binding in the LC was specific for the SERT, based on the rank order of affinity of compounds for inhibiting [(3)H]paroxetine binding in the LC, i.e. citalopram > imipramine > desipramine > mazindol. The binding of [(3)H]paroxetine to SERT and [(3)H]lazabemide to MAO-B were higher in the raphe nuclei than in the LC. Comparison of control subjects to major depressive subjects revealed no differences in the amount of [(3)H]paroxetine binding to SERT and [(3)H]lazabemide to MAO-B in the LC, as well as in the raphe nuclei. These findings imply that serotonergic innervation of the LC is intact in major depression.
去甲肾上腺素能系统和血清素能系统之间的神经化学失衡被认为是涉及情绪障碍的精神疾病病理生理学的基础。本研究旨在通过测量蓝斑(LC)区域中血清素能神经元而非去甲肾上腺素能神经元表达的两种蛋白质,来检验重度抑郁症患者中蓝斑的血清素能神经支配是否异常。在沿着蓝斑的头-尾范围的多个水平横向切割的组织切片中,以及在背侧中缝核的尾部,对来自精神正常的受试者和年龄匹配的重度抑郁症受试者,用放射自显影法测量了[(3)H]帕罗西汀与5-羟色胺转运体(SERT)的特异性结合以及[(3)H]拉扎贝胺与单胺氧化酶(MAO-B)的特异性结合。在测定条件下,基于化合物抑制[(3)H]帕罗西汀在蓝斑中结合的亲和力顺序,即西酞普兰>丙咪嗪>地昔帕明>马吲哚,[(3)H]帕罗西汀在蓝斑中的结合对SERT具有特异性。[(3)H]帕罗西汀与SERT的结合以及[(3)H]拉扎贝胺与MAO-B的结合在中缝核中高于在蓝斑中。对照受试者与重度抑郁症受试者的比较显示,在蓝斑以及中缝核中,[(3)H]帕罗西汀与SERT的结合量以及[(3)H]拉扎贝胺与MAO-B的结合量没有差异。这些发现表明,在重度抑郁症中蓝斑的血清素能神经支配是完整的。