DELAYED DESENSITIZATION OF ALPHA-2-ADRENOCEPTOR-MEDIATED PLATELET-AGGREGATION IN DEPRESSED-PATIENTS

After prolonged exposure to epinephrine, platelets are observed to des ensitize alpha2-adrenoceptor-mediated aggregation responses in vitro. Herein, this phenomenon was studied as a possible in vitro model for a lpha2-adrenoceptor dysregulation in depression. Platelet-rich plasmas obtained from 22 unipolar depressed patients and 25 healthy subjects w ere preincubated with 20 mumol/L of epinephrine for various lengths of time prior to stirring. By comparing the subsequent extents of aggreg ation, we observed significantly less desensitization at 4, 20, 30, or 60 minutes postepinephrine exposure (p less-than-or-equal-to .05) in depressed patients as compared to healthy controls. This blunted desen sitization appeared to be due to a delayed onset of desensitization du ring the first 0.5 to 2 minutes after epinephrine exposure, since ther eafter, the monoexponential desensitization rate did not differ in dep ressed patients, but the extent Of desensitization remained less as co mpared to healthy subjects. The extent of desensitization was correlat ed (r = - 0. 48, p = .02) with the density (B(max)) of the alpha2-adre noceptor high-affinity state, as detected in undesensitized platelet m embranes by pI-125-Clonidine binding. An elevation was also observed i n the density of nonadrenergic pI-125-clonidine-binding sites (putativ e imidazoline I1 sites) in platelet membranes from depressed patients compared to healthy control subjects. Following treatment with desipra mine, the patients (n = 15) displayed more normal (nonblunted) extents of desensitization of aggregation, and the B(max), values for the put ative I1 sites were at the levels of healthy controls. If similar aber rations exist in neurons of depressed patients, this may explain a dys regulation of the noradrenergic system believed to underlie depression .