Task difficulty determines the differential memory-impairing effects of EAA antagonists in gerbils

Excitatory amino acid antagonists (EAAAs) have been shown to disrupt learning and memory in a variety of cognitive tasks. EAAAs have been reported to produce differential effects on working memory (WM) and reference memory (RM) or to have no effect at all. Apparent selective effects of EAAAs on WM and/or RM may have been due to differences between the effects of competitive and noncompetitive EAAAs, dose selection, or to different task requirements for the WM and RM components. In the present experiments, we assessed the effects of a noncompetitive EAAA (MK-801), a competitive EAAA (CPP), and the muscarinic antagonist scopolamine in two cognitive tasks, the split-stem T-maze and the eight-arm radial maze. In these two tasks, the WM and the RM components differed in their relative degree of difficulty. Gerbils were trained on either the T-maze, where WM was more difficult than RM, or on the radial arm maze, where RM was more difficult than WM. In the T-maze, MK-801 (0.1 mg/kg, IP, 30 min prior), CPP (30.0 mg/kg, IP, 2 h prior) and scopolamine (0.3 mg/kg, IP, 30 min prior) impaired both WM and RM, but the magnitude of the impairing effect was statistically greater for the WM component, the more difficult of the two components. Lower doses of these three compounds produced either selective effects on WM or no effect at all. In the radial arm maze all three drugs impaired both components, but the magnitude of the impairing effect was statistically greater for the RM component, the more difficult of the two components.(ABSTRACT TRUNCATED AT 250 WORDS)