Elevated agonist binding to α2-adrenoceptors in the locus coeruleus in major depression

Background: Recent postmortem studies demonstrate disrupted neurochemistry of the noradrenergic locus coeruleus (LC) in major depression (MD). Increased levels of tyrosine hydroxylase and decreased levels of norepinephrine transporter implicate a norepinephrine deficiency in the LC in MD. Here we describe a study of alpha(2)-adrenoceptors in the LC and raphe nuclei of subjects with MD compared with psychiatrically normal control subjects. Methods: The specific binding of p-[I-125]iodoclonidine to alpha(2)-adrenoceptors was measured at multiple levels along the rostrocaudal extent of the LC in postmortem tissue from 14 control and 14 MD subjects. In addition, p-[I-125]iodoclonidine binding was measured in the dorsal and median raphe nuclei in the same tissue sections. Results: The specific binding of p-[I-125]iodoclonidine to alpha(2)-adrenoceptors was significantly elevated throughout the LC from MD compared with matched control subjects. No significant differences were observed in p-[I-125]iodoclonidine binding to alpha(2)-adrenoceptors in the raphe nuclei comparing MD and control subjects. Conclusions: Given that alpha(2)-adrenoceptors are upregulated in laboratory animals by treatment with drugs that deplete norepinephrine, our findings implicate a premortem deficiency of brain norepinephrine in the region of the locus coerideus in subjects with MD. (C) 2003 Society of Biological Psychiatry.