PHARMACOLOGICAL STUDIES OF A RAT SPATIAL DELAYED NONMATCH-TO-SAMPLE TASK AS AN ANIMAL-MODEL OF DEMENTIA

A variation of the delayed nonmatch-to-sample task in rats has recently been described in which the spatial positions of retractable levers are used as the sample and response cues. The pharmacology of this task has been investigated, with the aim of developing models relevant to the search for compounds active in dementia, particularly Alzheimer's disease. Scopolamine and atropine decreased the accuracy of responding. This was attenuated by physostigmine and THA. Mecamylamine, 8-OH DPAT, CPP, MK-801, and pentobarbital all produced marked accuracy deficits. Diazepam and sodium valproate affected accuracy rather less. Subthreshold doses of mecamylamine and scopolamine given together produced a significant accuracy deficit. All the drugs tested decreased the total trials performed. Prior satiation experiments demonstrated that this rate decrease in itself did not necessarily cause the decrease in accuracy. CPP and MK-801 appeared to produce the largest decrease in accuracy, with the least effect on rate. This selectivity, combined with the emerging role of the NMDA receptor complex in learning, memory, and dementia, encourages the development of this model or similar models in the search for compounds with the potential to treat dementia.