SELECTIVE INCREASE OF ALPHA(2A)-ADRENOCEPTOR AGONIST BINDING-SITES INBRAINS OF DEPRESSED SUICIDE VICTIMS

The alpha(2A)- and alpha(2C)-adrenoceptor subtypes were evaluated in p ostmortem brains from suicides with depression (n = 22), suicides with other diagnoses (n = 12), and controls (n = 26). Membrane assays with the antagonist [H-3]RX821002 (2-[H-3] methoxyidazoxan) suggested the presence of alpha(2A)-adrenoceptors in the frontal cortex and both alp ha(2C)-adrenoceptors and alpha(2A)-adrenoceptors in the caudate. The p roportions in caudate were similar in controls (alpha(2A), 86%; alpha( 2C), 14%), depressed suicides (alpha(2A), 91%; alpha(2C), 9%), and sui cides with other diagnoses (alpha(2A), 88%; alpha(2C), 12%). Autoradio graphy of [H-3]-RX821002 binding under alpha(2B/C)-adrenoceptor-maskin g conditions confirmed the similar densities of alpha(2A)-adrenoceptor s in the cortex, hippocampus, and striatum from controls and suicides. In the frontal cortex of depressed suicides, competition of [H-3]RX82 1002 binding by (-)adrenaline revealed a greater proportion (61 +/- 9% ) of alpha(2A)-adrenoceptors in the high-affinity conformation for ago nists than in controls (39 +/- 5%). Simultaneous analysis with the ago nists [H-3]clonidine and [H-3]UK14304 and the antagonist [H-3] RX82100 2 in the same depressed suicides confirmed the enhanced alpha(2A)-adre noceptor density when evaluated by agonist, but not by antagonist, rad ioligands. The results indicate that depression is associated with a s elective increase in the high-affinity conformation of the brain alpha (2A)-adrenoceptors.