Cholinergic modulation of spatial working memory of mice in radial maze performance: retention curve analysis.

Cholinergic modulation of the spatial working memory of mice was investigated in an eight-arm radial maze. The mice were trained to achieve a stable baseline level of performance, and the retention of spatial working memory was then examined by means of imposition of retention intervals of 45, 90, 180, and 360 min between choices four and five. The animals were removed from the apparatus during these intervals. The effects of oxotremorine (0.025-0.1 mg/kg, ip), physostigmine (0.025-0.1 mg/kg, ip), and scopolamine (0.1-0.4 mg/kg, ip) on the number of the correct responses after the various time intervals (5-8 choices) were studied. Mice received drug injections 30 min prior to the first four arm-choices before delay intervals (1-4 choices). The number of correct responses after the intervals decreased with the increased length of the retention interval. Oxotremorine and physostigmine exhibited dose-dependent stimulating effects of resistance to decreases in the number of correct responses, but scopolamine potentiated the decline in a dose-dependent manner. Significant interactions between the effects of cholinergic drugs and the length of retention over time were also observed. These observations indicate a cholinergic modulation of spatial working memory in mice engaged in radial maze performance, as assessed by means of retention curve analysis.