Effects of D-cycloserine, a positive modulator of N-methyl-D-aspartate receptors, and ST 587, a putative alpha-1 adrenergic agonist, individually andin 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 memor y processes, by examining the effects of individual and combined systemic a dministration 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 behavi our 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 workin g 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, imp roved retention of this task as reflected by the increased number of correc t choices before the first error during the retention phase. The combined a dministration 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 alo ne. Combinations of sub-threshold doses of ST 587 (50 or 75 mu g/kg) and DC S (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 ar m entries in a given time during the sampling phase. These findings suggest that the systemic administration of a positive modulator of the NMDA recep tor facilitates hippocampal-dependent memory functions, but that these effe cts are not enhanced by combined administration with an alpha-1 agonist, ev en though the alpha-1 agonist is effective when given alone. The results su pport the idea that NMDA receptors modulate both mnemonic and non-mnemonic functions in the brain.