Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test?

Abstract

Rationale: Microdialysis, binding and behavioural studies have shown that the dopaminergic system plays a role in antidepressant treatment. Objectives: 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 D₁ agonist SKF 38393, the D₁ antagonist SCH 23390, the D₂ agonist bromocriptine, the D₂ antagonist sulpiride, the D₃ agonist PD 128 907, or the D₃ 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.