Effect of combined treatment with imipramine and amantadine on the central dopamine D2 and D3 receptors in rats
by
Rogoz Z, Dlaboga D, Dziedzicka-Wasylewska M.
Department of Pharmacology, Institute of Pharmacology,
Polish Academy of Sciences, Krakow, Poland.
rogoz@if-pan.krakow.pl
J Physiol Pharmacol. 2003 Jun;54(2):257-70

ABSTRACT

In spite of intensive research, the problem of treating antidepressant-resistant depressive patients has not yet been solved. Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptors, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) than the treatment with either drug alone given. Since it has been suggested that dopamine receptors, among others, may play a role in anti-immobility effect of IMI, in the present study we examined the effect of AMA (10 mg/kg) and IMI (5 and 10 mg/kg) given separately or jointly, as a single dose or repeatedly (twice daily for 14 days) on the dopamine D(2) and D(3) receptors in the rat brain, using receptor autoradiography. Following repeated administration of AMA alone or given in combination with IMI (5 mg/kg), the binding of [(3)H]quinpirole (dopamine D(2)/D(3) receptors agonist) was increased, and similar changes were observed at the level of mRNA encoding dopamine D(2) receptors. We used [(3)H]7-OH-DPAT to selectively label the dopamine D(3) receptors. This experiment has shown that AMA given repeatedly did not induce statistically significant changes in the D(3) receptor binding, while IMI at both used doses, increased the [(3)H]7-OH-DPAT binding, and this effect was still observed after repeated joint administration of AMA with both doses of IMI. However, using both radioligands, we did not observe any synergistic or even additive effects in the binding studies after joint administration of AMA and IMI. Nevertheless, we can conclude that repeated administration of AMA, given together with IMI, induces the up-regulation of dopamine D(2) and D(3) receptors in the rat brain, and this effect may explain their synergistic action observed in the behavioral studies involving dopaminergic transmission.

MAO
NMDA
Opioids
Serotonin
Dopamine
Memantine
Amantadine
Antidepressants
Imipramine (Tofranil)
Amantadine (Symmetrel) : structure
Amantadine-induced Othello syndrome
Tricyclic antidepressants for depression

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