Differential expression of α 2-adrenoceptor vs. imidazoline binding sites in postmortem orbitofrontal cortex and amygdala of depressed subjects

Abstract

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 α 2-adrenergic agonist but possesses nearly equivalent affinity for non-adrenergic imidazoline binding sites (I-sites). Receptor autoradiography of [ 3H]-clonidine binding presented herein compares densities of α 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. [ 3H]-Clonidine binding to α 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 α 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 α 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 α 2AR towards I-site preponderance in depressed patients.