Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine

RATIONALE: The combination of atypical antipsychotic drugs in addition to serotonin reuptake inhibitors has recently proven to be beneficial in a number of neuropsychiatric disorders, such as major depression, schizophrenia, and obsessive-compulsive disorder. OBJECTIVES: To investigate the effects of an atypical antipsychotic drug in combination with a serotonin reuptake inhibitor on extracellular serotonin [5-HT]ex, and dopamine levels [DA]ex in different brain areas. METHODS: The effects of quetiapine (10 mg/kg) with fluvoxamine (10 mg/kg) on [5-HT]ex and [DA]ex were compared in the rat dorsal striatum, prefrontal cortex, nucleus accumbens (core and shell), and thalamus by means of microdialysis coupled to HPLC with electrochemical detection. RESULTS: Quetiapine had no significant effect on [DA]ex and [5-HT]ex levels in the prefrontal cortex and thalamus, but increased [DA]ex and [5-HT]ex levels in the dorsal striatum. In the accumbens, quetiapine increased [DA]ex levels and decreased [5-HT]ex levels. Fluvoxamine increased [5-HT]ex levels in all brain areas, and also increased [DA]ex levels in the striatum. The combination of quetiapine with fluvoxamine increased [DA]ex and [5-HT]ex levels in all brain areas compared with baseline. Although neither quetiapine nor fluvoxamine in monotherapy affected [DA]ex levels in the prefrontal cortex and thalamus, the combination produced a significant increase of [DA]ex levels in these two brain areas. CONCLUSIONS: The combination of quetiapine with fluvoxamine causes a synergistic dopamine increase in the prefrontal cortex and the thalamu