Differential expression of alpha2-adrenoceptor vs. imidazoline binding sites in postmortem orbitofrontal cortex and amygdala of depressed subjects.
Clonidine is a well established antihypertensive agent that is also used effectively to treat a variety of psychiatric disorders. Clonidine is a prototypic imidazoline compound that acts as an alpha(2)-adrenergic agonist but possesses nearly equivalent affinity for non-adrenergic imidazoline binding sites (I-sites). Receptor autoradiography of [(3)H]-clonidine binding presented herein compares densities of alpha(2)-adrenoceptors and I-sites (under a noradrenergic-mask) in Brodmann's area 47 of the left orbitofrontal cortex (OFC) and in six amygdaloid nuclei of subjects with major depression (n=12) vs. controls with no psychiatric history (n=11). Postmortem diagnoses were made from psychiatric interviews with next-of-kin. [(3)H]-Clonidine binding to alpha(2)-adrenoceptors in each of six OFC layers was lower, although not reaching statistical significance in any one layer by multivariate analysis, in depressives vs. control subjects. Binding to I-sites was conversely higher in depressives compared to control OFC layers, but did not reach statistical significance alone. However, the ratios of alpha(2)-adrenoceptor : I-sites in all six layers of OFC of depressed subjects were nearly half that of control subjects (P<0.008). In amygdalas from a different group of depressed patients there were no changes in alpha(2)-adrenoceptors or I-sites, or their ratios, compared with controls. The results support previous western blot data indicating a cortex-selective shift away from alpha(2)AR towards I-site preponderance in depressed patients.
Piletz
John E
JE
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA. johnpiletz@yahoo.com
Ordway
Gregory A
GA
Rajkowska
Grazyna
G
Zhu
He
H
Klimek
Violeta
V
Swilley
Sharonda
S
Duncan
Betty J
BJ
May
Warren
W
Halaris
Angelos E
AE
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000378:metabolism*; D001345:Autoradiography; D001665:Binding Sites; D003000:Clonidine / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D054755:Imidazoline Receptors; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000032:analysis / Q000378:metabolism*; D011955:Receptors, Drug / Q000032:analysis / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D003000:Clonidine