ANTIDEPRESSANT DRUGS GIVEN REPEATEDLY CHANGE THE BINDING OF THE DOPAMINE D-2 RECEPTOR AGONIST, [H-3] N-0437, TO DOPAMINE D-2 RECEPTORS IN THE RAT-BRAIN

The effects of antidepressants given in a single dose or repeatedly (1 0 mg/kg p.o., twice daily, 14 days) on binding to dopamine D-2 recepto rs in the striatum and limbic forebrain of Wistar male rats were studi ed. [H-3]N-0437, propyl-N-(2-triofuranyl)-2'-ethylamino)-5-hydroxy- 1, 2,3,4-tetrahydronaphthalene), a dopamine D-2 receptor agonist, was use d as a ligand. Already a single dose of imipramine and fluoxetine caus ed a statistically significant decrease in the affinity of the ligand for dopamine D-2 receptors in the striatum, but only at 72 h after dru g administration. Also at 72 h after the single dose of mianserin a si gnificant increase in the density of dopamine D-2 receptors was observ ed. Repeated imipramine, amitriptyline and mianserin increased the aff inity for dopamine D-2 receptors in the striatum and in the limbic for ebrain. Repeated fluoxetine increased that affinity in the striatum, b ut decreased it in the limbic forebrain. The density of dopamine D-2 r eceptors was increased by the repeated administration of the antidepre ssants studied in the limbic forebrain, but was not changed in the str iatum. The results obtained in the present study are in good agreement with the previously reported enhancement of behavioural responsivenes s to dopamine and dopamine stimulants (dopamine D-2 up-regulation) evo ked by repeated treatment with antidepressants.