Selective increase of α(2A)-adrenoceptor agonist binding sites in brains of depressed suicide victims

Abstract

The α(2A) and α(2C)-adrenoceptor subtypes were evaluated in postmortem brains from suicides with depression (n = 22), suicides with other diagnoses (n = 12), and controls (n = 26). Membrane assays with the antagonist [3H]RX821002 (2-[3H]methoxyidazoxan) suggested the presence of α(2A)- adrenoceptors in the frontal cortex and both α(2C)-adrenoceptors and α(2A)- adrenoceptors in the caudate. The proportions in caudate were similar in controls (α(2A), 86%; α(2C), 14%), depressed suicides (α(2A), 91%; α(2C), 9%), and suicides with other diagnoses (α(2A), 88%; α(2C), 12%). Autoradiography of [3H]-RX821002 binding under α(2B/C)-adrenoceptor- masking conditions confirmed the similar densities of α(2A)-adrenoceptors in the cortex, hippocampus, and striatum from controls and suicides. In the frontal cortex of depressed suicides, competition of [3H]RX821002 binding by (-)-adrenaline revealed a greater proportion (61 ± 9%) of α(2A)- adrenoceptors in the high-affinity conformation for agonists then in controls (39 ± 5%). Simultaneous analysis with the agonists [3H]clonidine and [3H] UK14304 and the antagonist [3H]RX821002 in the same depressed suicides confirmed the enhanced α(2A)-adrenoceptor density when evaluated by agonist, but not by antagonist, radioligands. The results indicate that depression is associated with a selective increase in the high-affinity conformation of the brain α(2A)-adrenoceptors.