Isoxsuprine; a possible interaction with cholinergic neurones in the rat brain

Abstract

The origins of the cholinergic innervation of the rat neocortex were studied by means of neurotoxic amino acid lesions and neurochemical analysis. A crude topographical pattern of projections from the cholinergic perikarya within the magnocellular nuclei of the basal forebrain to the allocortex were determined. The more rostrally located cells of the medial septal complex project to the hippocampus,
whilst the more caudally located neurones of the nucleus basalis project to the ipsilateral parietal cortex and the amygdala. No evidence for a cholinergic projection to the cortex from the medial septum was found. The neurochemical specificity and neuroanatomical selectivity of ibotenic acid lesions of the ventral globus pallidus were studied using both neurochemical and histological techniques. Similarities between the degeneration produced by these lesions and the neurodegenerative disorder Alzheimer's dementia are discussed, in respect of a possible 'animal model' for this disorder.
The effects of isoxsuprine, a drug reported to alleviate the symptoms of senile dementia, on the uptake of oxygen in vitro, and [3H] 2-deoxyglucose in vivo into discrete areas of rat brain were studied. In vivo pretreatment with isoxsuprine was found to stimulate oxygen uptake into rat brain cortex slices. No significant effect on [3H] 2-deoxyglucose uptake could be determined. The effects of isoxsuprine pretreatment oncholine acetyltransferase activity and high affinity choline uptake were also studied.
These results are again discussed in terms of the currently available pharmacotherapy for Alzheimer's dementia.

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