DOSE-RELATED IMPAIRMENT OF SPATIAL-LEARNING BY INTRAHIPPOCAMPAL SCOPOLAMINE - ANTAGONISM BY ONDANSETRON, A 5-HT3 RECEPTOR ANTAGONIST

To study the role of hippocampal muscarinic receptors in spatial learn ing, various doses of scopolamine were injected bilaterally into the C AI region of the dorsal hippocampus of rats trained in a two-platform spatial discrimination task. Scopolamine administered 10 min before ea ch training session at doses ranging from 3.75 to 15 mu g/ul impaired choice accuracy, had no effect on choice latency and increased the err ors of omission only with 7.5 mu g on day 1 and with 15 mu g on days 1 and 2 of training. No dose affected choice accuracy or latency of a n on-spatial visual discrimination task. A subcutaneous dose of 1 mu g/k g ondansetron, a 5-HT3 receptor antagonist, 30 min before each trainin g session prevented the impairment of choice accuracy by intrahippocam pal 3.75 mu g scopolamine but 0.1 mu g/kg ondansetron had no such effe ct. No dose of ondansetron by itself modified the acquisition of spati al learning. The results suggest that relatively low doses of scopolam ine in the dorsal hippocampus selectively impair the acquisition of a spatial discrimination task, and that blockade of 5-HT3 receptors prev ents the deficit caused by the muscarinic antagonist. The utility of t he deficit of spatial learning induced by intrahippocampal scopolamine for modelling some aspects of memory disturbances in Alzheimer's dise ase is discussed.