title: Effect of risperidone on the fluoxetine-induced changes in extracellular dopamine, serotonin and noradrenaline in the rat frontal cortex.
abstract: BACKGROUND
  Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors, in the treatment of drug resistant depression. The aim of our study was to understand the mechanism of the clinical efficacy of a combination of fluoxetine (FLU) and risperidone (RIS) in drug-resistant depression. We studied the effect of FLU and RIS, given separately or jointly on the extracellular levels of dopamine (DA), serotonin (5-HT) and noradrenaline (NA) in the rat frontal cortex.
  
  
  METHODS
  Animals were given single intraperitoneal injections of RIS at a doses of 0.1 or 1 mg/kg and FLU at a dose of 10 mg/kg. The release of DA, 5-HT and NA in the rat frontal cortex was investigated using microdialysis in freely moving animals. The extracellular level of DA, 5-HT and NA was assayed by HPLC with coulochemical detection.
  
  
  RESULTS
  RIS (0.1 and 1 mg/kg) and FLU (10 mg/kg) increased the extracellular level of cortical DA, 5-HT and NA. Co-treatment of both drugs was more effective in increasing DA release than administration of each of the drugs alone at doses of RIS 1 mg/kg and FLU 10 mg/kg. Co-treatment of FLU and RIS 0.1 mg/kg was more potent than FLU alone, while the effect of joint injection of FLU and RIS 1 mg/kg was stronger than RIS 1 mg/kg alone on 5-HT release. The combination of FLU with both doses of RIS was not effective in increasing NA release as compared to drugs given alone.
  
  
  CONCLUSIONS
  Our data indicate that the effect of the combined administration of RIS and FLU on DA and 5-HT release in the rat frontal cortex may be of crucial importance to the pharmacotherapy of drug resistant depression.
authors.affiliation: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. rogoz@if-pan.krakow.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kamińska
authors.forename: Krystyna
authors.initials: K
authors.lastname: Gołembiowska
authors.forename: Zofia
authors.initials: Z
authors.lastname: Rogóż
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D004298:Dopamine; D005473:Fluoxetine; D009638:Norepinephrine; D018967:Risperidone; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors