Antidepressant drugs given repeatedly change the binding of the dopamine D2 receptor agonist, [3H]N-0437, to dopamine D2 receptors in the rat brain.
The effects of antidepressants given in a single dose or repeatedly (10 mg/kg p.o., twice daily, 14 days) on binding to dopamine D2 receptors in the striatum and limbic forebrain of Wistar male rats were studied. [3H]N-0437, (2-(N[2,3(n)-3H]propyl-N-(2-thiofuranyl)-2'-ethylamino) -5-hydroxy-1,2,3,4-tetrahydronaphthalene), a dopamine D2 receptor agonist, was used as a ligand. Already a single dose of imipramine and fluoxetine caused a statistically significant decrease in the affinity of the ligand for dopamine D2 receptors in the striatum, but only at 72 h after drug administration. Also at 72 h after the single dose of mianserin a significant increase in the density of dopamine D2 receptors was observed. Repeated imipramine, amitriptyline and mianserin increased the affinity for dopamine D2 receptors in the striatum and in the limbic forebrain. Repeated fluoxetine increased that affinity in the striatum, but decreased it in the limbic forebrain. The density of dopamine D2 receptors was increased by the repeated administration of the antidepressants studied in the limbic forebrain, but was not changed in the striatum. The results obtained in the present study are in good agreement with the previously reported enhancement of behavioural responsiveness to dopamine and dopamine stimulants (dopamine D2 up-regulation) evoked by repeated treatment with antidepressants.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Dziedzicka-Wasylewska
M
M
Rogoz
R
R
Rogóz
Z
Z
Skuza
G
G
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018491:Dopamine Agonists / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism*; D013876:Thiophenes / Q000378:metabolism*; D015854:Up-Regulation
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D005473:Fluoxetine; D000639:Amitriptyline; D008803:Mianserin; C047508:rotigotine; D007099:Imipramine