Concurrent administration of subeffective doses of scopolamine and MK-801 produces a short-term amnesia for the elevated plus-maze in mice

Amnesic properties of scopolamine, a muscarinic receptor antagonist, and MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, were evaluated in mice by means of the elevated plus-maze test. In this test, transfer latency, the time mice took to move from the open arm to the enclosed arm, was used as an index of learning and memory. The 3-day pretreatment training dramatically decreased transfer latencies. On the 4th day, the retention trial was performed 30 min after the intraperitoneal injection of scopolamine (Experiment 1) or MK-801 (Experiment 2). The hoses of 0.25 and 0.5 mg/kg of scopolamine as well as the doses of 0.1, 0.15, 0.2 and 0.4 mg/kg of MK-801 significantly prolonged the transfer latency as compared with both that in the saline-treated group and that measured on the 3rd day. In Experiment 3, subthreshold doses of these two drugs given in combination (which were ineffective when given alone: scopolamine 0.25 mg/kg, MK-801 0.075 mg/kg) significantly prolonged the transfer latency on the fourth day. However, an amnesic effect of scopolamine plus MK-801 was transient. On the 5th day, no differences in the transfer latency were found. This finding clearly indicates that there is a close relationship between cholinergic and glutamatergic systems and that both systems play an important role in a spatial orientation of mice on the elevated plus-maze. (C) 1998 Elsevier Science B.V. All rights reserved.