Effects of strychnine-insensitive glycine receptor antagonists and sigma agents on working memory performance: comparison with dizocilpine and scopolamine.

The strychnine insensitive glycine receptor antagonists (+/-) HA 966 (2.5, 3.5, 4.25 and 5.0mg/kg) and 7 chlorokynurenic acid (5.0, 10.0, and 15.0mg/kg), the putative sigma agents NPC 16377 (5.0 and 8.0mg/kg), BMY 14802 (5.0, 7.5 and 10.0mg/kg), and ifenprodil (5.0 and 7.0mg/kg) and the reference agents scopolamine and dizocilpine [(+) MK 801] were evaluated in a nonspatial delayed matching to sample working memory task in rats. (+/-) HA 966 impaired accuracy at the longest retention interval and decreased response probability measures. 7-Chlorokynurenic acid was essentially without effect. The noncompetitive NMDA antagonist dizocilpine reduced accuracy at all retention intervals, decreased the probability of a choice response and increased the probability of an intertrial interval response. The anticholinergic agent scopolamine selectively reduced accuracy at the longest retention interval but did not affect other performance measures. Sigma agents decreased response probability measures but did not affect accuracy at any retention interval. The results support the notion that sigma agents, glycine antagonists and NMDA antagonists produce different effects in cognitive tasks including working memory performance.