Effects of D-cycloserine and cycloleucine, ligands for the NMDA-associated strychnine-insensitive glycine site, on brain-stimulation reward and spontaneous locomotion.

D-Cycloserine (DCS) binds with high affinity to the glycine site associated with the NMDA receptor in rat brain. Systemic injections of DCS have been reported to facilitate performance on learning tasks, possibly by promoting long-term changes at the NMDA receptor complex. In the present study, DCS failed to affect spontaneous locomotor activity or variable-interval self-stimulation response rate. Cycloleucine, a competitive antagonist of glycine at the glycine site, produced a brief depression of self-stimulation, but only after relatively large doses which were not antagonised by injection of DCS in the dose reported to be optimal for the facilitation of learning. Improvements in learning and retention reported after administration of DCS are therefore unlikely to be accounted for by nonassociative motivational, or performance, factors.