Spatial learning deficit after NMDA receptor blockade and state-dependency

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocil pine (MK-801) (0.08 and 0.12 mg/kg, i.p.) was used to examine whether spati al memory is learned state dependently. Rats pre-treated with drug or salin e were trained for 9 days in an eight-arm radial maze, in which four arms w ere baited. On the tenth day MK-801-treated rats were injected with saline and one group of saline-treated rats were injected with MK-801 (0.12 mg/kg) while another received saline. Performance of spatial memory was analysed for state-dependency. Neither rats treated with 0.08 mg/kg nor 0.12 mg/kg o f MK-801 for 9 days were impaired in recall of spatial memory under saline. However, MK-801 impaired acquisition of spatial memory, with deficits in w orking memory and less marked deficits in reference memory. Motor activity (speed) was enhanced at both doses. Thus, learning under NMDA receptor bloc kade does not necessarily produce a condition that impedes the expression o f the learning task under a different condition. (C) 1999 Lippincott Willia ms & Wilkins.