Elevated agonist binding to alpha2-adrenoceptors in the locus coeruleus in major depression
Related Experiment Video
Updated: Sep 27, 2026

Localization of the Locus Coeruleus in the Mouse Brain
Published on: March 7, 2019
Gregory A Ordway1, Jane Schenk, Craig A Stockmeier
1Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.
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.
More Related Videos
07:56A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
08:15Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
Published on: June 6, 2025
Related Concept Videos
Drugs Affecting Neurotransmitter Release or Uptake
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
G Protein-coupled Receptors
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Antidepressant Drugs: MAOIs and Other Agents
Drugs Affecting Neurotransmitter Synthesis