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


OBJECTIVE
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 thalamus.
Denys
Damiaan
D
Department of Psychiatry, The Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. d.a.j.p.denys@azu.nl
Klompmakers
André A
AA
Westenberg
Herman G M
HG
D000818:Animals; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004338:Drug Combinations; D004357:Drug Synergism; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D000069348:Quetiapine Fumarate; D051381:Rats; D017208:Rats, Wistar
D003987:Dibenzothiazepines; D004338:Drug Combinations; D000069348:Quetiapine Fumarate; D016666:Fluvoxamine; D004298:Dopamine