Selective Increase of α2A‐Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims

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Abstract
The α2A‐ and α2C‐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 α2A‐adrenoceptors in the frontal cortex and both α2C‐adrenoceptors and α2A‐adrenoceptors in the caudate. The proportions in caudate were similar in controls (α2A, 86%; α2C, 14%), depressed suicides (α2A, 91%; α2C, 9%), and suicides with other diagnoses (α2A, 88%; α2C, 12%). Autoradiography of [3H]RX821002 binding under α2B/C‐adrenoceptor‐masking conditions confirmed the similar densities of α2A‐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 α2A‐adrenoceptors in the high‐affinity conformation for agonists than 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 α2A‐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 α2A‐adrenoceptors.

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