CHRONIC DESIPRAMINE AND FLUOXETINE DIFFERENTIALLY AFFECT EXTRACELLULAR DOPAMINE IN THE RAT PREFRONTAL CORTEX

The effect of chronic administration of desipramine or fluoxetine (10 mg/kg IP once a day for 2 weeks) on extracellular noradrenaline, serot onin and dopamine in the rat prefrontal cortex was studied by transcer ebral microdialysis. Chronic desipramine increased extracellular norad renaline and dopamine by three-fold as compared to saline controls. Ac ute challenge with 10 mg/kg desipramine increased by more than three-f old extracellular noradrenaline and dopamine in saline controls, but f ailed further to increase extracellular noradrenaline and dopamine in rats chronically administered desipramine. Chronic fluoxetine more tha n doubled the extracellular concentrations of serotonin but failed to change the extracellular concentrations of dopamine as compared to sal ine controls. Challenge with 5 mg/kg fluoxetine while almost doubling extracellular serotonin and dopamine concentrations in saline controls , failed further to increase extracellular serotonin and did not chang e extracellular dopamine in rats chronically exposed to fluoxetine. In contrast, challenge with 10 mg/kg desipramine normally increased extr acellular dopamine in rats chronically exposed to fluoxetine. Therefor e, chronic fluoxetine is associated with normal presynaptic dopamine t ransmission in the prefrontal cortex as a result of tolerance to fluox etine-induced increase of extracellular dopamine, in contrast, chronic desipramine is associated with an increase of pre-synaptic dopamine t ransmission in the prefrontal cortex up to a level that cannot be furt her elevated by acute desipramine challenge. The results suggest that prefrontal cortex dopamine plays a different role in the antidepressan t properties of desipramine and fluoxetine.