Stimulation of dopamine D-2 but not D-1 receptors reduces immobility time of rats in the forced swimming test: implication for antidepressant activity.

The involvement of dopamine D-1 and D-2 receptor mechanisms was investigated in the forced swimming test with rats. d,1-Sulpiride, a D-2 receptor antagonist, reported to reduce desipramine-induced anti-immobility, did not alter the brain levels of desipramine. In addition, the anti-immobility effect of desipramine was not antagonized by SCH 23390, a D-1 receptor antagonist. Amineptine (20 mg/kg i.p., 60 min before testing), a dopamine uptake blocker, and LY171555 (0.2 mg/kg i.p., 60 min before testing), a dopaminergic D-2 stimulant reduced immobility time in the forced swimming test, but benserazide + 1-DOPA (200 mg/kg p.o., 45 min before testing), which increases dopamine release, or SKF 38393A (20 mg/kg s.c., 60 min before testing), a D-1 agent, did not. The anti-immobility effect but not the stereotypy was increased following chronic (21 days) LY171555 (0.1 and 0.2 mg/kg i.p.) treatment. The effect of acute or repeated (7 days) LY171555 (0.2 mg/kg i.p.) treatment was antagonized by 1-sulpiride (50 mg/kg i.p., 90 min before testing), a D-2 receptor antagonist. Neither SKF 38393A (20 mg/kg s.c., 60 min before testing) nor SCH 23390 (0.05 mg/kg s.c., 30 min before testing) modified the acute anti-immobility effect of LY171555 (0.2 mg/kg i.p.) SCH 23390 (0.025 and 0.05 mg/kg) increased the immobility time at doses which decreased motor activity. The increase in immobility time brought about by SCH 23390 was not antagonized by SKF 38393A (20 mg/kg). The findings indicate that activation of dopamine D-2 receptors could reduce immobility time.