Effects of dopamine receptor agonists on passive avoidance learning in mice: interaction of dopamine D₁ and D₂ receptors

The present study examined the effects of dopamine D₁ and D₂ receptor agonists on the acquisition stage of passive avoidance learning and on locomotor activity in mice. The D₂ agonist, RU 24213 (1-10 mg/kg s.c.), and the non-selective agonist, apomorphine (0.3-3 mg/kg s.c.), but not the D₁ agonist, SKF 38393 (1-10 mg/kg s.c.), impaired learning and activated locomotion. RU 24213 (1 mg/kg s.c.) was more effective in impairing learning than in activating locomotion. The concurrent administration of SKF 38393 (10 mg/kg i.p.) and RU 24213 (1 and 3 mg/kg s.c.) produced a synergistic effect in both behavioral situations. The D₁ antagonist, SCH 23390 (0.025 mg/kg i.p.), slightly inhibited the effects of apomorphine and of the combination of SKF 38393 and RU 24213 on learning but not on locomotion. The D₂ antagonist, (-)-sulpiride (40 mg/kg i.p.), completely blocked these effects in both situations. These results suggest that dopamine receptor agonists impair passive avoidance learning through the D₂ receptor, and that D₁ and D₂ receptors act synergistically in this impairment, as they do in their effects on locomotion. The involvement of D₁ and D₂ receptors is qualitatively similar in each of these behaviors, although some small differences may exist.