Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test?
BACKGROUND
Microdialysis, binding and behavioural studies have shown that the dopaminergic system plays a role in antidepressant treatment.


OBJECTIVE
The present study determined whether the antidepressant-like effects of selective serotonin reuptake inhibitors measured in the mouse forced swimming test are mediated via dopamine receptors.


METHODS
Male Swiss mice were randomly assigned to groups of 24 animals and injected IP with citalopram, fluoxetine, fluvoxamine, sertraline, or paroxetine alone or in combination with the dopamine D(1)agonist SKF 38393, the D(1) antagonist SCH 23390, the D(2) agonist bromocriptine, the D(2) antagonist sulpiride, the D(3) agonist PD 128 907, or the D(3) antagonist nafadotride.


RESULTS
The anti-immobility effects of paroxetine, fluvoxamine and citalopram were increased by co-administration of SKF 38393 (0.5 and 2 mg/kg), SCH 23390 (0.06 mg/kg), bromocriptine (0.5 and 2 mg/kg) or PD 128 907 (1 and 2 mg/kg), and were attenuated by SCH 23390 (0.5 mg/kg). The anti-immobility effects of paroxetine and fluvoxamine were also increased with sulpiride (0.5 and 2 mg/kg). The anti-immobility effect of fluoxetine was increased by SKF 38393 (2 mg/kg) and PD 128 907(1 and 2 mg/kg) co-administration. The anti-immobility effect of sertraline (16 mg/kg) was increased by SKF 38393 (0.5 mg/kg), bromocriptine (2 mg/kg) and PD 128 907 (2 mg/kg) and the effect of sertraline (2 mg/kg) was increased by bromocriptine (2 mg/kg). The anti-immobility effect of paroxetine (4 mg/kg) was increased by nafadotride (2 mg/kg).


CONCLUSIONS
These data indicate that the antidepressant activity of various SSRIs involves different dopamine receptor subtypes and that the serotoninergic and dopaminergic systems interact with each other.
Renard
C E
CE
EA Neurobiologie de l'anxiété et de la dépression, Faculté de Medecine, BP 53508, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France.
Fiocco
A J
AJ
Clenet
F
F
Hascoet
M
M
Bourin
M
M
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D013550:Swimming
D000928:Antidepressive Agents; D004298:Dopamine; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017367:Selective Serotonin Reuptake Inhibitors