Effect of antidepressant drugs administered repeatedly on the dopamine D3 receptors in the rat brain.

Previous studies have indicated that antidepressant drugs displaying different pharmacological profiles, administered repeatedly, increase the locomotor hyperactivity induced by various dopaminomimetics, among others by quinpirole. As this drug, according to a recent study, shows high affinity not only for dopamine D2 but also for dopamine D3 receptors, the question arises if dopamine D3 receptors are involved in the increase in quinpirole-elicited locomotor hyperactivity induced by repeated treatment with antidepressant drugs. In the present study we administered imipramine, amitriptyline, citalopram and mianserin (in a dose of 10 mg/kg p.o., twice a day, 14 days) to male Wistar rats and then (+/-)-7-OH-DPAT (7-hydroxy-dipropylaminotetralin), a dopamine D3 receptor agonist, was given (3 mg/kg s.c.). Hyperlocomotion induced by (+/-)-7-OH-DPAT was significantly increased by repeated administration of antidepressant drugs. The receptor autoradiography technique with [3H]7-OH-DPAT as a radioligand was applied to measure the effects of antidepressant drugs treatment on the dopamine D3 receptors in the islands of Calleja and in the shell of the nucleus accumbens septi, which are brain regions with highly selective expression of dopamine D3 receptors. The biochemical studies indicated that in both examined brain regions there was an increase in the binding of [3H]7-OH-DPAT following the repeated administration of antidepressant drugs. In some cases this increase was also observed after the acute administration of antidepressants. The results obtained in the present study indicate that antidepressant drugs administered repeatedly enhance the responsiveness of dopamine D3 receptors, probably via an increase in the density of these receptors. This mechanism is probably similar to that observed already in the case of dopamine D2 receptors. Therefore it is hypothesized that dopamine D3 receptors are also involved in the increased responsiveness to dopamine D3 receptor agonists observed after antidepressants.