Back to Search
Start Over
Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex.
- Source :
-
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2000 Sep; Vol. 23 (3), pp. 250-62. - Publication Year :
- 2000
-
Abstract
- To understand the mechanism of the clinical efficacy of olanzapine and fluoxetine combination therapy for treatment-resistant depression (TRD), we studied the effects of olanzapine and other antipsychotics in combination with the selective serotonin uptake inhibitors fluoxetine or sertraline on neurotransmitter release in rat prefrontal cortex (PFC) using microdialysis. The combination of olanzapine and fluoxetine produced robust, sustained increases of extracellular levels of dopamine ([DA](ex)) and norepinephrine ([NE](ex)) up to 361 +/- 28% and 272 +/- 16% of the baseline, respectively, which were significantly greater than either drug alone. This combination produced a slightly smaller increase of serotonin ([5-HT](ex)) than fluoxetine alone. The combination of clozapine or risperidone with fluoxetine produced less robust and persistent increases of [DA](ex) and [NE](ex). The combination of haloperidol or MDL 100907 with fluoxetine did not increase the monoamines more than fluoxetine alone. Olanzapine plus sertraline combination increased only [DA](ex). Therefore, the large, sustained increase of [DA](ex), [NE](ex), and [5-HT](ex) in PFC after olanzapine-fluoxetine treatment was unique and may contribute to the profound antidepressive effect of the olanzapine and fluoxetine therapy in TRD.
- Subjects :
- Animals
Antipsychotic Agents pharmacokinetics
Benzodiazepines
Brain metabolism
Drug Synergism
Extracellular Space metabolism
Fluoxetine pharmacokinetics
Male
Microdialysis
Olanzapine
Pirenzepine pharmacokinetics
Pirenzepine pharmacology
Prefrontal Cortex drug effects
Rats
Rats, Sprague-Dawley
Serotonin metabolism
Selective Serotonin Reuptake Inhibitors pharmacokinetics
Stimulation, Chemical
Antipsychotic Agents pharmacology
Dopamine metabolism
Fluoxetine pharmacology
Norepinephrine metabolism
Pirenzepine analogs & derivatives
Prefrontal Cortex metabolism
Selective Serotonin Reuptake Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0893-133X
- Volume :
- 23
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10942849
- Full Text :
- https://doi.org/10.1016/S0893-133X(00)00119-6