Elevated agonist binding to alpha2-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 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.
Ordway
Gregory A
GA
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Schenk
Jane
J
Stockmeier
Craig A
CA
May
Warren
W
Klimek
Violetta
V
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000378:metabolism*; D000328:Adult; D000345:Affinity Labels; D000368:Aged; D001344:Autopsy; D001345:Autoradiography; D003000:Clonidine / Q000031:analogs & derivatives*; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019275:Radiopharmaceuticals; D011903:Raphe Nuclei / Q000378:metabolism / Q000473:pathology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000345:Affinity Labels; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2; C053113:4-iodoclonidine; D003000:Clonidine