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Antidepressant drugs given repeatedly change the binding of the dopamine D2receptor agonist, [3H]N-0437, to dopamine D2receptors in the rat brain

European Journal of Pharmacology
Publication Date
DOI: 10.1016/0014-2999(96)00123-9
  • Antidepressant
  • Repeated Treatment
  • Dopamine D2Receptor Binding
  • [3H]N-0437


Abstract The effects of antidepressants given in a single dose or repeatedly (10 mg/kg p.o., twice daily, 14 days) on binding to dopamine D 2 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 D 2 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 D 2 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 D 2 receptors was observed. Repeated imipramine, amitriptyline and mianserin increased the affinity for dopamine D 2 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 D 2 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 D 2 up-regulation) evoked by repeated treatment with antidepressants.

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