DIFFERENTIAL-EFFECTS OF COMPOUNDS THAT ACT AT STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS IN A PUNISHMENT PROCEDURE

The anxiolytic and memory-impairing effects of compounds that act at s trychnine-insensitive (SI) glycine receptors were examined and compare d with those of a competitive N-methyl-D-aspartate antagonist, 2-amino -7-phosphonoheptanoic acid (AP7); a use-dependent channel blocker, diz ocilpine; and a benzodiazepine agonist, diazepam (DZP). Mice were trai ned to avoid a dark compartment and their latencies to step through we re measured either within 1 hr after training in the presence of the d rug (to assess the anxiolytic effects) or 24 hr after pre- or post-tra ining treatment (to assess the effects on learning and memory). Post-t raining administration of the glycinergic compounds 1-aminocyclopropan ecarboxylic acid, 7-chlorokynurenic acid and D-cycloserine reduced ste p-through latencies when testing was performed 30 min after drug treat ment and within 1 h after training. Latencies were unaltered by these glycinergic compounds when testing was performed 24 hr later. Similar results were obtained with AP7 and DZP. In contrast, an amnesic dose o f pentylenetetrazole reduced latencies both within 1 and 24 hr after t raining. Pretreatment with glycine abolished the reduction in latencie s observed with SI glycine receptor ligands 1 hr after training but di d not antagonize the reduction produced by AP7. Pretraining administra tion of SI glycine receptor ligands did not alter step-through latenci es measured 24 hr later. In contrast, under these same conditions, AP7 , dizocilpine and DZP produced a significant reduction in latencies. T hese results demonstrate that compounds that act at SI glycine recepto rs do not impair learning and memory at doses that are anxiolytic in a single-trial punishment paradigm.