Effects of antidepressant drugs on the dopamine D-2/D-3 receptors in the rat brain differentiated by agonist and antagonist binding - an autoradiographic analysis

In the present study the effect of antidepressant drugs on the density of d opamine D-2/D-3 receptors in the rat forebrain was examined using autoradio graphy, since this technique provides the appropriate anatomical resolution . Male Wistar rats were treated with three various antidepressant drugs: im ipramine, citalopram and mianserin in a dose of 10 mg/kg p.o., acutely (sin gle dose) or repeatedly (twice a day for 14 days). To estimate the distribu tion of D-2/D-3 receptors, we chose following radioligands: [H-3]raclopride , a non-selective antagonist of D-2/D-3 receptors, and [H-3]quinpirole, a n on-selective D-2/D-3 agonist. When [H-3]raclopride was used as a radioligan d, no significant differences in the density of D-2/D-3 receptors were obse rved after administration of the investigated drugs. However, following rep eated administration of imipramine, citalopram and mianserin, a significant increase in the binding of [H-3]quinpirole was observed, both in the nucle us caudatus and nucleus accumbens septi. In some cases the increase of [H-3 ]quinpirole binding was also observed after acute treatment with antidepres sant drugs. Thus, using an agonist as a radioligand, we were able to see up regulation of dopamine D2/D3 receptors in the rat forebrain following admin istration of antidepressant drugs, which might be interpreted as the bioche mical correlative for the postsynaptic dopamine D-2/D-3 receptor supersensi tivity observed in previous behavioral studies.