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

Abstract 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 α 2 -adrenoceptors in the LC and raphe nuclei of subjects with MD compared with psychiatrically normal control subjects. Methods The specific binding of p-[ 125 I]iodoclonidine to α 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-[ 125 I]iodoclonidine binding was measured in the dorsal and median raphe nuclei in the same tissue sections. Results The specific binding of p-[ 125 I]iodoclonidine to α 2 -adrenoceptors was significantly elevated throughout the LC from MD compared with matched control subjects. No significant differences were observed in p-[ 125 I]iodoclonidine binding to α 2 -adrenoceptors in the raphe nuclei comparing MD and control subjects. Conclusions Given that α 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 coeruleus in subjects with MD.