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

Autor: Craig A. Stockmeier, Warren L. May, Violetta Klimek, Jane Schenk, Gregory A. Ordway
Rok vydání: 2003
Předmět:
Zdroj: Biological Psychiatry. 53:315-323
ISSN: 0006-3223
DOI: 10.1016/s0006-3223(02)01728-6
Popis: 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.
Databáze: OpenAIRE