Effects of antidepressant drugs on the dopamine D2/D3 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 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.
Rogoz
R
R
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Dziedzicka-Wasylewska
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001345:Autoradiography; D015283:Citalopram / Q000494:pharmacology; D018491:Dopamine Agonists / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects*; D011485:Protein Binding; D019257:Quinpirole / Q000378:metabolism; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects; D012457:Salicylamides / Q000378:metabolism; D013997:Time Factors
D000928:Antidepressive Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D015283:Citalopram; D019257:Quinpirole; D008803:Mianserin; D020891:Raclopride; D007099:Imipramine