Pridopidine Reverses Phencyclidine-Induced Memory Impairment

Abstract

Pridopidine is in clinical trials for Huntington's diseasetreatment. Originally developedas a dopamine D2receptor (D2R) ligand, pridopidine displays about 100-fold higheraffinity for the sigma-1 receptor (sigma-1R). Interestingly, pridopidine slows diseaseprogression and improves motor function in Huntington's disease model mice and,in preliminarily reports, Huntington's disease patients.The present study examinedthe anti-amnesic potential of pridopidine. Thus, memory impairment was produced inmice by administration of phencyclidine (PCP, 10 mg/kg/day) for 10 days, followedby 14 days' treatment with pridopidine (6 mg/kg/day), or saline. Finally, novel objectrecognition performance was assessed in the animals. Mice receiving PCP andsaline exhibited deficits in novel object recognition, as expected, while pridopidinetreatment counteracted PCP-induced memory impairment. The effect of pridopidine wasattenuated by co-administration of the sigma receptor antagonist, NE-100 (10 mg/kg).Our results suggest that pridopidine exerts anti-amnesic and potentially neuroprotectiveactions. These data provide new insights into the therapeutic potential of pridopidine asa pro-cognitive drug.