title: Effects of chronic fluoxetine treatment on serotonin 1B receptor-induced deficits in delayed alternation.
abstract: BACKGROUND
  Obsessive-compulsive disorder (OCD) patients show overactivation of the orbitofrontal cortex and deficits in cognitive tasks that require proper orbitofrontal functioning including delayed alternation tests of spatial working memory. We recently showed that OCD-like behavior is induced in mice by activating orbitofrontal serotonin 1B receptors (5-HT1Bs). However, the role of 5-HT1Bs in delayed alternation remains unclear.
  
  
  OBJECTIVE
  We examined the effects of 5-HT1B receptor activation on delayed alternation task (DAT) performance. We also assessed the ability of an effective OCD treatment, fluoxetine, to prevent 5-HT1B-induced deficits in DAT performance.
  
  
  METHODS
  Mice were tested on the DAT after acute treatment with saline, 3 or 6 mg/kg RU24969 (5-HT1B/1A agonist), 0.3 or 3 mg/kg 8-OH-DPAT (5-HT1A agonist), or co-injection with 3 mg/kg RU24969 and 5 mg/kg GR127935 (5-HT1B/1D antagonist). Separate mice were pretreated chronically (28 days) with 10 mg/kg fluoxetine and then tested on the DAT after acute treatment with 3 mg/kg RU24969, 0.3 mg/kg 8-OH-DPAT, or saline.
  
  
  RESULTS
  Both doses of RU24969 decreased accuracy and increased latency on the DAT, and GR127935 blocked RU24969-induced effects on accuracy. The 0.3 mg/kg 8-OH-DPAT did not affect the DAT performance, whereas 3 mg/kg increased omissions on the DAT. Finally, RU24969-induced DAT deficits were absent in fluoxetine-pretreated mice.
  
  
  CONCLUSIONS
  We show that 5-HT1B receptor activation disrupts DAT performance in mice, and chronic fluoxetine pretreatment blocks these 5-HT1B-induced deficits. Our findings suggest that 5-HT1B receptors play an important role in modulating orbitofrontal-dependent delayed alternation. Moreover, 5-HT1B-induced DAT deficits may provide a mouse model for DAT deficits in OCD.
authors: Department of Psychology, Wittenberg University, Springfield, OH 45504, USA.
authors: Nancy S
authors: NS
authors: Woehrle
authors: Stephanie J
authors: SJ
authors: Klenotich
authors: Naseem
authors: N
authors: Jamnia
authors: Emily V
authors: EV
authors: Ho
authors: Stephanie C
authors: SC
authors: Dulawa
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000627:therapeutic use*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013647:Task Performance and Analysis; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors
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