Effect of chronic administration of antidepressants on alpha 2-adrenoceptors in the locus coeruleus and its projection fields in rat brain determined by quantitative autoradiography.
The density of alpha 2-adrenoceptors, using 3H-idazoxan as the radioligand, was determined by quantitative autoradiography in the locus coeruleus and in 13 noradrenergic projection fields following chronic administration of drugs acting on noradrenergic and/or serotonergic neurons. Protriptyline, an inhibitor of the uptake or norepinephrine, and mianserin, an alpha 2-adrenoceptor antagonist, reduced the binding of 3H-idazoxan only in the locus coeruleus. Phenelzine, an inhibitor of both type A and type B monoamine oxidase (MAO), reduced the binding of 3H-idazoxan in the locus coeruleus and in several areas with noradrenergic innervation from tegmental cell bodies. Clorgyline, a selective inhibitor of type A MAO, had no effect. Of the two selective inhibitors of serotonin uptake, citalopram caused a modest increase in binding only in one terminal field area, whereas sertraline had no effect. Although these antidepressants did not produce consistent effects on alpha 2-adrenoceptors, protriptyline, mianserin, and phenelzine were similar in that they all decreased the binding of 3H-idazoxan in the locus coeruleus without widely affecting its binding in the coerulean terminal fields. Deprenyl, a selective inhibitor of type B MAO, the only drug in this study without proven antidepressant efficacy, differed from all other drugs in that it decreased the binding of 3H-idazoxan both in the locus coeruleus as well as in most terminal fields with primarily coerulean noradrenergic innervation.
Kovachich
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GB
Department of Veterans Affairs Medical Center, Department of Psychiatry, Philadelphia, Pennsylvania 19104.
Frazer
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A
Aronson
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CE
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D001921:Brain / Q000187:drug effects; D004146:Dioxanes / Q000378:metabolism; D019329:Idazoxan; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D019329:Idazoxan