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

摘要

The density of α2-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 of norepinephrine, and mianserin, an α2-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 α2-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.