Fluoxetine Increases Extracellular Dopamine in the Prefrontal Cortex by a Mechanism Not Dependent on Serotonin

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Abstract
: Fluoxetine at 10 and 25 mg/kg increased (167 and 205%, respectively) the extracellular dopamine concentration in the prefrontal cortex, whereas 25 (but not 10) mg/kg citalopram raised (216%) dialysate dopamine. No compound modified dialysate dopamine in the nucleus accumbens. The effect of 25 mg/kg of both compounds on cortical extracellular dopamine was not significantly affected by 300 mg/kg p‐chlorophenylalanine (PCPA) (fluoxetine, saline, 235% ; PCPA, 230% ; citalopram, saline, 179% ; PCPA, 181%). PCPA depleted tissue and dialysate serotonin by ~90 and 50%, respectively, and prevented the effect of fluoxetine and citalopram on dialysate serotonin (fluoxetine, saline, 246% ; PCPA, 110% ; citalopram, saline, 155% ; PCPA, 96%). Citalopram significantly raised extracellular serotonin from 0.1 to 100 μM (251‐520%), whereas only 10 and 100 μM increased dialysate dopamine (143‐231%). Fluoxetine similarly increased extracellular serotonin (98‐336%) and dopamine (117‐318%). PCPA significnatly reduced basal serotonin and the effects of 100 μM fluoxetine (saline, 272% ; PCPA, 203%) and citalopram (saline, 345% ; PCPA 258%) on dialysate serotonin but did not modify their effect on dopamine (fluoxetine, saline, 220% ; PCPA, 202% ; citalopram, saline, 191% ; PCPA, 211%). The results clearly show that the effects of fluoxetine and of high concentrations of citalopram on extracellular dopamine do not depend on their effects on serotonin.

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