SPATIAL WORKING AND REFERENCE MEMORY IN RATS BRED FOR AUTONOMIC SENSITIVITY TO CHOLINERGIC STIMULATION - ACQUISITION, ACCURACY, SPEED, AND EFFECTS OF CHOLINERGIC DRUGS

Rat lines were selected by breeding for sensitivity to signs of autono mic stimulation (hypothermia, loss of body weight, and reduced water i ntake) induced by the cholinesterase inhibitor diisopropyl fluorophosp hate (DFP). These lines have since been maintained for 10 generations by continued selection for hypothermic responsiveness to the muscarini c agonist oxotremorine. The sensitive rats (Flinders Sensitive Line, F SL) differ from the resistant rats (Flinders Resistant Line, FRL) both neurochemically and behaviorally, particularly in aversively motivate d test situations in which response speed is assessed. This study was conducted to determine whether the selected differences in cholinergic autonomic sensitivity would be expressed as differences in cognitive ability based on choice accuracy in appetitive tasks. The working and reference memory of rats of these two strains was thus assessed using operant delayed matching-to-position/visual discrimination (DMTP/VD) a nd the radial-arm maze. A Long-Evans (L-E) reference group was include d in the DMTP/VD study. FSL rats responded more slowly than the other rats during acquisition of both tasks, but showed no differences in re sponse accuracy either during acquisition or during asymptotic perform ance of either task. In addition, challenges with muscarinic and nicot inic antagonists and agonists [scopolamine (0.06-1.0 mg/kg), pilocarpi ne (1.0-4.0 mg/kg), mecamylamine (1.0-10.0 mg/kg), and nicotine (0.1-0 .3 mg/kg)] demonstrated predicted differences in sensitivity among the lines only on performance measures such as response latency and trial completion. Counter to prediction, the sensitivity of the FRL rats to the ability of scopolamine to reduce matching accuracy was lower than those of the L-E and FSL rats. Thus selection based upon physiologica l endpoints related to cholinergic autonomic homeostasis did not produ ce analogous differences in cognitive function in rats. (C) 1995 Acade mic Press, Inc.