Distribution of alpha 2-adrenoceptors in the human locus coeruleus

Recent reports of specific topographic patterns of cell loss in the locus coeruleus (LC) in psychiatric and neurologic disorders underscores the need for detailed neurochemical analyses of this cell group. In this study, the anatomical distribution of alpha 2-adrenoceptors and its relationship to the distribution of noradrenergic neurons in the human LC was studied. Quantitative autoradiography was used to assess the binding of [125I]p-iodoclonidine ([125I]PIC) to alpha 2-adrenoceptors coordinately with counts of neuromelanin-containing cells in tissue sections cryocut at 10-13 levels along the rostrocaudal axis of the LC. Pontine brain tissue was obtained postmortem from 7 subjects dying of natural or accidental causes, ranging in age from 26 to 78 years. Both the binding of [125I]PIC and number of neuromelanin-containing cells were differentially distributed along the LC axis (P < 0.01) with almost identical topographical patterns. The highest concentration of binding and the greatest number of neuromelanin-containing cells per section occurred near the middle portion of the nucleus. There was a significant correlation between the number of neuromelanin-containing cells per section and the specific binding of [125I]PIC at any particular level of the LC (r2 = 0.56; P < 0.0001). The highest and lowest amounts of [125I]PIC binding in the LC were observed in the youngest and oldest subjects, respectively, and this trend was parallelled by a significant negative correlation between the number of neuromelanin-containing cells at a given level and age (r2 = 0.85; P < 0.003). The uneven distribution of alpha 2-adrenoceptors in the LC demonstrates the importance of anatomical specificity when performing quantitative studies of LC protein chemistry in psychiatric and neurologic disorders.