Effects of D-cycloserine, a positive modulator of N-methyl-D-aspartate receptors, and ST 587, a putative alpha-1 adrenergic agonist, individually and in combination, on the non-delayed and delayed foraging behaviour of rats assessed in the radial arm maze

The present study investigated whether alpha-1 adrenergic and glutamatergic N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms interact in memory processes, by examining the effects of individual and combined systemic administration of ST 587, a putative alpha-1 agonist, and D-cycloserine (DCS), a partial agonist at the glycine-B binding site of the NMDA receptor, on the performance of rats in non-delayed and delayed (4-6 h) foraging behaviour in the radial arm maze task, using the delayed non-matching to sample (DNMTS) version. The results indicated that DCS (5.0 mg/kg) decreased working memory errors, i.e. the number of re-entries into the previously visited arms during the sampling phase. In addition, both ST 587 (100 mu g/kg) and DCS (10 mg/kg), when administered alone 30 min before a sampling phase, improved retention of this task as reflected by the increased number of correct choices before the first error during the retention phase. The combined administration of ST 587 and DCS, however, did not lead to better retention in the DNMTS task compared with the administration of each of the drugs alone. Combinations of sub-threshold doses of ST 587 (50 or 75 mu g/kg) and DCS (5.0 or 7.5 mg/kg) also did not improve retention in this task. DCS (5.0 or 7.5 mg/kg) increased activity as indicated by the increased number of arm entries in a given time during the sampling phase. These findings suggest that the systemic administration of a positive modulator of the NMDA receptor facilitates hippocampal-dependent memory functions, but that these effects are not enhanced by combined administration with an alpha-1 agonist, even though the alpha-1 agonist is effective when given alone. The results support the idea that NMDA receptors modulate both mnemonic and non-mnemonic functions in the brain.