Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine
- 178 Downloads
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.
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.
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.
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.
The combination of quetiapine with fluvoxamine causes a synergistic dopamine increase in the prefrontal cortex and the thalamus.
KeywordsDopamine Serotonin Microdialysis Schizophrenia Obsessive–compulsive disorder Pharmacotherapy
- Adityanjee, Schulz SC (2002) Clinical use of quetiapine in disease states other than schizophrenia. J Clin Psychiatry 63[Suppl 13]:32–38Google Scholar
- Di Matteo V, Cacchio M, Di Giulio C, Di Giovanni G, Esposito E (2002a) Biochemical evidence that the atypical antipsychotic drugs clozapine and risperidone block 5-HT(2C) receptors in vivo. Pharmacol Biochem Behav 71:607–613Google Scholar
- Di Matteo V, Cacchio M, Di Giulio C, Esposito E (2002b) Role of serotonin(2C) receptors in the control of brain dopaminergic function. Pharmacol Biochem Behav 71:727–734Google Scholar
- Gobert A, Rivet JM, Lejeune F, Newman-Tancredi A, Adhumeau-Auclair A, Nicolas JP, Cistarelli L, Melon C, Millan MJ (2000) Serotonin(2C) receptors tonically suppress the activity of mesocortical dopaminergic and adrenergic, but not serotonergic, pathways: a combined dialysis and electrophysiological analysis in the rat. Synapse 36:205–221CrossRefPubMedGoogle Scholar
- Hillert A, Maier W, Wetzel H, Benkert O (1992) Risperidone in the treatment of disorders with a combined psychotic and depressive syndrome-a functional approach. Pharmacopsychiatry 25:213–217Google Scholar
- Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O’Laughlin IA, Meltzer HY (2001) 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 76:1521–1531PubMedGoogle Scholar
- Paxinos G, Watson C (1994) The rat brain in stereotaxic coordinates. San Diego, CAGoogle Scholar
- Tohen M, Jacobs TG, Grundy SL, McElroy SL, Banov MC, Janicak PG, Sanger T, Risser R, Zhang F, Toma V, Francis J, Tollefson GD, Breier A (2000) Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group. Arch Gen Psychiatry 57:841–849PubMedGoogle Scholar
- Zhang W, Perry KW, Wong DT, Potts BD, Bao J, Tollefson GD, Bymaster FP (2000) Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology 23:250–262CrossRefPubMedGoogle Scholar