Neuroanatomical structures involved in the action of the 5-HT 3 antagonist ondansetron: A 2-deoxyglucose autoradiographic study in the rat

Abstract

Local cerebral glucose utilization following the acute administration of the 5-HT 3 receptor antagonist ondansetron (0.01–1.0 mg/kg) was determined using [ 14C]2-deoxyglucose quantitative Ondansetron effected alterations in 13 of the 66 brain areas analyzed including limbic, auditory and visual structures. In the majority of these 13 regions ondansetron was only effective at reducing glucose use compared to control values at a dose of 0.01 mg/kg. Thus in limbic and related areas (CA 2 and CA 3 fields of the hippocampus, lateral habenula and septal nucleus) glucose utilization was reduced by 15–21%. Similar reductions (18–20%) were apparent in primary auditory and visual areas (auditory cortex, medial geniculate and visual cortex). However, with the exception of the ventromedial thalamic nucleus (14% reduction) glucose use in extrapyramidal and sensory motor areas was unchanged. Following larger doses of ondansetron (0.1 and 1.0 mg/kg), there was no change in cerebral glucose utilization relative to control values, with the exception of the median raphe. In this structure local cerebral glucose utilization was significantly increased (P < 0.05) following administration of 1.0 mg/kg ondansetron relative to the lower dose of 0.01 mg/kg. Changes in glucose use did not always reflect areas of high 5-HT 3 receptor density. Thus, although cerebral glucose use was reduced in hippocampal layers, it was unchanged in the entorhinal cortex and the area postrema. These data suggest that under these experimental conditions ondansetron produces modest changes in glucose utilization which are primarily confined to limbic structures and those involved in sensory processing.