L-DOPA and Nonselective DA Agonists Are Effective in Restoring Locomotion in DDD Mice

<p>DAT-KO mice were placed in the locomotor activity chamber and 30 min later were treated with αMT (250 mg/kg IP) and 1 h after αMT were challenged with single or multiple doses of a drug (interval between treatments is 1 h). L-DOPA itself (A) or in combination with carbidopa (B–D) effectively restored locomotion in DDD mice, as revealed by the significant effect of L-DOPA at doses 100 and 200 mg/kg IP, or combinations of L-DOPA/carbidopa at doses 20/20, 50/20, and 50/50 mg/kg, IP (analysis of total distance traveled for 1 h after each dose of the drug; <i>p</i> < 0.05, two-tailed Mann-Whitney <i>U</i> test versus respective values in saline-treated DDD mice; data not shown). Nonselective DA receptor agonists, apomorphine (E) at doses 2 and 3 mg/kg SC, and pergolide (F) at doses 5, 10, and 20 mg/kg IP, induced locomotion in DDD mice (analysis of total distance traveled for 1 h after each dose of the drug; <i>p</i> < 0.05, two-tailed Mann-Whitney <i>U</i> test, versus respective values in saline-treated DDD mice; data not shown). D2 DA receptor agonists bromocriptine (G), quinpirole (H), and D1 DA receptor agonist (+)-SKF81297 (I) were not effective, but the combinations of D1 and D2 DA agonists (+)-SKF81297 plus quinpirole at doses 5/1 and 10/5 mg/kg IP, induced significant locomotion in DDD mice (analysis of total distance traveled for 1 h after each treatment; <i>p</i> < 0.05, two-tailed Mann-Whitney <i>U</i> test versus respective values in saline-treated DDD mice; data not shown). Experiments were performed in 6–12 mice per group.