Decreased platelet alpha-2 adrenoceptor density in major depression: Effects of tricyclic antidepressants and fluoxetine

Background: It has been suggested that major depression is accompanied by a subsensitivity of central alpha 2-adrenoceptors (alpha 2-ARs) and, consequ ently, by an impaired negative feedback on the presynaptic catecholaminergi c neuron, which, in turn, may induce a disinhibition of noradrenergic outpu t and norepinephrine release in response to any activation. Methods: The maximum number of platelet binding sites (Bmax) and their affi nity for [H-3]-rauwolscine, a selective alpha 2-AR antagonist, were measure d in unmedicated and medicated major depressed patients and in normal volun teers. Specific binding was defined as that inhibited by idazoxan, another alpha 2-AR antagonist. Results: Unmedicated major depressed patients had significantly decreased p latelet [H-3]-rauwolscine binding Bmax values compared to normal volunteers . [H-3]-rauwolscine binding K-d values did not differ significantly between unmedicated major depressed patients and normal controls. [H-3]-rauwolscin e binding Bmax or K-d values. [H-3]-rauwolscine binding Bmax values were si gnificantly greater in men than in women. Conclusions: The results suggest that i) major depression is accompanied by decreased platelet alpha 2-AR density; and the ii) subchronic treatment wi th tricyclic antidepressants, but not fluoxetine, results in a decreased af finity of rauwolscine for platelet alpha 2-ARs. Biol Psychiatry 1999; 45:27 8-284 (C) 1999 Society of Biological Psychiatry.