Selective Neurotoxic Lesions of Descending Serotonergic and Noradrenergic Pathways in the Rat

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Abstract
The ability of neurotoxic substances to induce selective lesions of the descending monoaminergic pathways in rats was investigated. Saline, 6-hydroxydopamine [6-OHDA], 5,6-dihydroxytryptamine [5,6-DHT] or 5,7-dihydroxytryptamine [5,7-DHT] were administered into the lumbar subarachnoid space through a chronically indwelling catheter. The lesions were evaluated 2-3 wk later by in vitro uptake of [3H]noradrenaline [norepinephrine, NE] and [14C]5-hydroxytryptamine [5-HT] into synaptosomal preparations from the frontal cortex, brainstem, cervical spinal cord and lumbar spinal cord of each animal. There was no difference in uptake between saline-injected and noncatheterized controls and no significant changes in cortical uptake after any of the treatments (dose range of neurotoxins: 0.6-80 .mu.g). In the lumbar spinal cord, 6-OHDA (5-80 .mu.g) reduced the [3H]NE uptake by .apprx. 90% with no effects on [14C]5-HT uptake, whereas 5,6-DHT reduced the uptake of [14C] 5-HT by 90% (20-80 .mu.g). [3H]NE uptake was unaffected by lower doses of 5,6-DHT but fell by 45-55% after 40-80 .mu.g. 5,7-DHT (10-80 .mu.g) reduced [3H]NE uptake by 90-95% and [14C]5-HT uptake by .apprx. 80% (5-80 .mu.g) in the lumbar cord. Intrathecal administration of suitable doses of neurotoxins may produce extensive selective lesions of descending noradrenergic and serotonergic pathways.