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 learning, various doses of scopolamine were injected bilaterally into the CA1 region of the dorsal hippocampus of rats trained in a two-platform spatial discrimination task. Scopolamine administered 10 min before each training session at doses ranging from 3.75 to 15 micrograms/microliter impaired choice accuracy, had no effect on choice latency and increased the errors of omission only with 7.5 micrograms on day 1 and with 15 micrograms on days 1 and 2 of training. No dose affected choice accuracy or latency of a non-spatial visual discrimination task. A subcutaneous dose of 1 microgram/kg ondansetron, a 5-HT3 receptor antagonist, 30 min before each training session prevented the impairment of choice accuracy by intrahippocampal 3.75 micrograms scopolamine but 0.1 microgram/kg ondansetron had no such effect. No dose of ondansetron by itself modified the acquisition of spatial learning. The results suggest that relatively low doses of scopolamine in the dorsal hippocampus selectively impair the acquisition of a spatial discrimination task, and that blockade of 5-HT3 receptors prevents the deficit caused by the muscarinic antagonist. The utility of the deficit of spatial learning induced by intrahippocampal scopolamine for modelling some aspects of memory disturbances in Alzheimer's disease is discussed.