title: Serotonin transporter and MAO-B levels in monoamine nuclei of the human brainstem are normal in major depression.
abstract: 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.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216, USA.
authors.forename: Violetta
authors.initials: V
authors.lastname: Klimek
authors.forename: Gary
authors.initials: G
authors.lastname: Roberson
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Ordway
mesh_terms: D000328:Adult; D000368:Aged; D001345:Autoradiography; D015306:Biogenic Monoamines / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism; D010848:Picolinic Acids / Q000378:metabolism; D011869:Radioligand Assay; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D010848:Picolinic Acids; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human; C059303:lazabemide