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.

• Authors: Gregory A Ordway, Jane Schenk, Craig A Stockmeier, Warren May, Violetta Klimek
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 53 Issue 4 Pg. 315-23 (Feb 15 2003) ISSN: 0006-3223 [Print] United States
• PMID: 12586450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-Agonists
• Affinity Labels
• Radiopharmaceuticals
• Receptors, Adrenergic, alpha-2
• 4-iodoclonidine
• Clonidine

Topics

• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-Agonists (metabolism)
• Adult
• Affinity Labels
• Aged
• Autopsy
• Autoradiography
• Clonidine (analogs & derivatives)
• Depressive Disorder, Major (metabolism, pathology)
• Female
• Humans
• Locus Coeruleus (metabolism, pathology)
• Male
• Middle Aged
• Radiopharmaceuticals
• Raphe Nuclei (metabolism, pathology)
• Receptors, Adrenergic, alpha-2 (metabolism)