Effect of fluoxetine on the spontaneous electrical activity of fronto-cortical neurons

The effect of fluoxetine on spontaneous extracellular activity of fronto-cortical neurons of chloral hydrate-anesthetized rats was investigated. Fluoxetine significantly increased the basal firing rate of cortical neurons in a dose-dependent manner (0.1-1000 micrograms kg-1 i.v.), with a maximum excitatory effect of 53% at 1000 micrograms kg-1. Selective destruction of ascending serotoninergic pathways induced by intracerebroventricular injections of 150 micrograms 5,7-dihydroxytryptamine, in desipramine-pretreated rats, antagonized the excitatory effect of fluoxetine. The present results suggest that fluoxetine significantly increases the electrical activity of the fronto-cortical neurons acting on serotoninergic uptake mechanisms localized at the level of raphe nuclei.