Selective Increase of α2A-Adrenoceptor Agonist Binding Sites in Brains of Depressed Suicide Victims |
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Authors: | Luis F Callado J Javier Meana Bernardo Grijalba Angel Pazos †Magdalena Sastre †Jesús A García-Sevilla |
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Institution: | Department of Pharmacology, University of the Basque Country, Leioa, Bizkaia;; Department of Physiology and Pharmacology, University of Cantabria, Santander;and; Laboratory of Neuropharmacology, Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain |
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Abstract: | 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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Keywords: | α2-Adrenoceptor subtypes Depression Human brain Suicide Frontal cortex |
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