Increased noradrenaline efflux induced by local infusion of fluoxetine in the rat frontal cortex

In microdialysis experiments in vivo, local infusion of either the selective serotonin reuptake inhibitor, fluoxetine, or the selective noradrenaline uptake inhibitor, desipramine, increased noradrenaline efflux in rat frontal cortex. Synaptosomal uptake of [H-3]noradrenaline was used to test whether inhibition of uptake could contribute to this effect of fluoxetine. Low concentrations of fluoxetine were less effective than desipramine at inhibiting [H-3]noradrenaline uptake; both compounds were more potent than the selective serotonin reuptake inhibitor, citalopram. To investigate whether this inhibition of uptake involved an action on noradrenergic neurones, experiments compared the effects of a noradrenergic lesion, induced by the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), on the inhibition of uptake by fluoxetine, desipramine and citalopram. The lesion reduced [H-3]noradrenaline uptake in the presence of fluoxetine and citalopram but increased it in the presence of desipramine. The results suggest both that inhibition of noradrenaline uptake could contribute to the actions of fluoxetine and that a non-noradrenergic mechanism is a target for this action.