title: Effect of co-treatment with fluoxetine or mirtazapine and risperidone on the active behaviors and plasma corticosterone concentration in rats subjected to the forced swim test.
abstract: BACKGROUND
  Several clinical reports have postulated a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants in treatment-resistant depression.
  
  
  METHODS
  The present study aimed to examine the effect of treatment with fluoxetine or mirtazapine, given separately or jointly with risperidone, on active behavior and plasma corticosterone level in male Wistar rats subjected to the forced swim test (FST).
  
  
  RESULTS
  The obtained results showed that fluoxetine (5 mg/kg), mirtazapine (5 and 10 mg/kg) or risperidone (0.05 and 0.1 mg/kg) did not change the active behavior of rats in the FST. However, co-treatment with fluoxetine (10 mg/kg) and risperidone (0.1 mg/kg) induced an antidepressant-like effect in that test because it significantly increased the swimming time and decreased the immobility time, while combined treatment with mirtazapine at 5 and 10 mg/kg and risperidone at 0.05 and 0.1 mg/kg evoked a significant increase in the swimming time and also climbing, and decreased the immobility time. WAY 100635 (a 5-HT(1A) receptor antagonist) at a dose of 0.1 mg/kg inhibited the antidepressant-like effect induced by co-administration of fluoxetine or mirtazapine and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined treatment with fluoxetine or mirtazapine and risperidone failed to enhance the exploratory activity of rats. Co-treatment with fluoxetine or mirtazapine and risperidone did not reduce the stress-induced increase in plasma corticosterone concentration in animals subjected to the FST.
  
  
  CONCLUSIONS
  The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of fluoxetine and mirtazapine in the FST (but does not normalize the stress-induced increase in corticosterone level in these rats), and that 5-HT(1A) receptors may play some role in these effects.
authors: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. rogoz@if-pan.krakow.pl
authors: Zofia
authors: Z
authors: Rogóż
authors: Marcin
authors: M
authors: Kabziński
authors: Witold
authors: W
authors: Sadaj
authors: Paulina
authors: P
authors: Rachwalska
authors: Anna
authors: A
authors: Gądek-Michalska
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013550:Swimming
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D003345:Corticosterone; D005473:Fluoxetine; D008803:Mianserin; D000078785:Mirtazapine; D044282:Receptor, Serotonin, 5-HT1A; D018967:Risperidone; D058829:Serotonin 5-HT1 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors