Effects of the Dopamine Stabilizer, Pridopidine, on Basal and Phencyclidine-Induced Locomotion: Role of Dopamine D2 and Sigma-1 Receptors

摘要

Background: Pridopidine, a compound in clinical trials for Huntington's disease treatment,was originally synthesized as a dopamine D2 receptor (D2R) ligand, but later found to possess higheraffinity for the sigma-1 receptor (S1R). However, the putative contributions of D2R and S1R to thebehavioral profile of acutely administered pridopidine have not been investigated.Objective: The present study sought to compare the effects of acute pridopidine on wild-type vs. D2Rand S1R knockout mice, at high (60 mg/kg) and low (6 mg/kg) doses.Method: Pridopidine effects on basal and phencyclidine-induced locomotor activity was measured inthe open field test. Additionally, the actions of pridopidine on prepulse inhibition was measured inanimals treated with saline or phencyclidine.Results: Whereas inhibition of spontaneous and phencyclidine-induced locomotion was readily observedat 60 mg/kg pridopidine, neither locomotor stimulation in habituated mice, nor any effects onprepulse inhibition were detected upon pridopidine treatment. Surprisingly, inhibition of spontaneouslocomotion was unaffected by both D2R and S1R deletion.Conclusion: The present results suggest the involvement of additional targets, besides D2R and S1R,in mediating locomotor inhibition by pridopidine.