Elevated agonist binding to alpha2-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 alpha2-adrenoceptors in the LC and raphe nuclei of subjects with MD compared with psychiatrically normal control subjects. METHODS:The specific binding of p-[125I]iodoclonidine to alpha2-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-[125I]iodoclonidine binding was measured in the dorsal and median raphe nuclei in the same tissue sections. RESULTS:The specific binding of p-[125I]iodoclonidine to alpha2-adrenoceptors was significantly elevated throughout the LC from MD compared with matched control subjects. No significant differences were observed in p-[125I]iodoclonidine binding to alpha2-adrenoceptors in the raphe nuclei comparing MD and control subjects. CONCLUSIONS:Given that alpha2-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.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Ordway GA,Schenk J,Stockmeier CA,May W,Klimek V

doi

10.1016/s0006-3223(02)01728-6

subject

Has Abstract

pub_date

2003-02-15 00:00:00

pages

315-23

issue

4

eissn

0006-3223

issn

1873-2402

pii

S0006322302017286

journal_volume

53

pub_type

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