Effects of antidepressant drugs on the dopamine D2/D3 receptors in the rat brain differentiated by agonist and antagonist binding – an autoradiographic analysis

Abstract

In the present study the effect of antidepressant drugs on the density of dopamine D₂/D₃ receptors in the rat forebrain was examined using autoradiography, since this technique provides the appropriate anatomical resolution. Male Wistar rats were treated with three various antidepressant drugs: imipramine, citalopram and mianserin in a dose of 10 mg/kg p.o., acutely (single dose) or repeatedly (twice a day for 14 days). To estimate the distribution of D₂/D₃ receptors, we chose following radioligands: [³H]raclopride, a non-selective antagonist of D₂/D₃ receptors, and [³H]quinpirole, a non-selective D₂/D₃ agonist. When [³H]raclopride was used as a radioligand, no significant differences in the density of D₂/D₃ receptors were observed after administration of the investigated drugs. However, following repeated administration of imipramine, citalopram and mianserin, a significant increase in the binding of [³H]quinpirole was observed, both in the nucleus caudatus and nucleus accumbens septi. In some cases the increase of [³H]quinpirole binding was also observed after acute treatment with antidepressant drugs. Thus, using an agonist as a radioligand, we were able to see upregulation of dopamine D₂/D₃ receptors in the rat forebrain following administration of antidepressant drugs, which might be interpreted as the biochemical correlative for the postsynaptic dopamine D₂/D₃ receptor supersensitivity observed in previous behavioral studies.