Competitive and non-competitive NMDA receptor antagonists in spatial learning tasks

Abstract

The effects of the competitive N-methyl-D-aspartate (NMDA) receptor antagonists, CGP37849 (3 or 6 mg/kg i.p.) and its ethyl ester CGP39551 (5 or 15 mg/kg i.p.) and of the non-competitive NMDA receptor antagonist, dizocilpine (0.16 mg/kg; i.p.) on acquisition by rats of different spatial orientation tasks in an 8-arm radial maze were evaluated. Neither of the CGP compounds influenced locomotor activity during spontaneous alternation, only dizocilpine increased the number of arm entries (locomotion). Preferred angles between consecutive arm entries were changed by the high doses of CGP37849 (6 mg/kg), CGP39551 (15 mg/kg) and dizocilpine (0.16 mg/kg). The high doses of both CGP compounds as well as dizocilpine produced impairments in the acquisition of an egocentric orientation task and an allocentric reversal task indicated by an increased number of arm entries and re-entries. Such amnesic effects did not occur after administration of low doses of CGP37849 (3 mb/kg) and CGP39551 (5 mg/kg), doses which are sufficient to produce anticonvulsant and anticataleptic effects. In contrast, the non-competitive NMDA receptor antagonist, dizocilpine, produced amnesic effects over the entire behaviourally effective dose range.