title: Postnatal fluoxetine-evoked anxiety is prevented by concomitant 5-HT2A/C receptor blockade and mimicked by postnatal 5-HT2A/C receptor stimulation.
abstract: BACKGROUND
  Postnatal treatment with the selective serotonin reuptake inhibitor fluoxetine, evokes anxiety and depressive behavior in rodent models in adulthood. We examined the role of serotonin 2A (5-HT2A), serotonin 2C (5-HT2C) and serotonin 1A (5-HT1A) receptors, implicated in the development of anxiety, in the behavioral consequences of postnatal fluoxetine (PNFlx).
  
  
  METHODS
  Control and PNFlx rat pups received concomitant treatment with the 5-HT2A/C receptor antagonist, ketanserin, the 5-HT2A receptor antagonist, MDL100907, the 5-HT2C receptor antagonist, SB242084, or the 5-HT1A receptor antagonist, WAY-100635, and were tested for behavior in adulthood. The effect of postnatal treatment with the 5-HT2A/C receptor agonist, DOI, on anxiety behavior was examined in adulthood.
  
  
  RESULTS
  Postnatal 5-HT2A/C receptor blockade prevented PNFlx-evoked anxiety, attenuated depressive behavior, and normalized specific gene expression changes in the prefrontal cortex. Postnatal, selective 5-HT2A receptor antagonist treatment blocked PNFlx-evoked anxiety and depressive behavior, whereas 5-HT2C receptor antagonist treatment prevented anxiety but not depressive behavior. Postnatal 5-HT2A/C receptor stimulation was sufficient to evoke anxiety in adulthood. Serotonin 1A receptor blockade did not alter PNFlx-evoked anxiety but resulted in anxiety in control animals, an effect attenuated by concomitant 5-HT2A/C receptor blockade.
  
  
  CONCLUSIONS
  Postnatal fluoxetine-evoked anxiety and depressive behavior, as well as specific gene expression changes in the prefrontal cortex, were prevented by 5-HT2A/C receptor blockade. Adult anxiety was evoked by either 5-HT2A/C receptor stimulation or 5-HT1A receptor blockade of naive control pups. Our findings implicate serotonin 2 receptors in the development of perturbed emotionality following PNFlx and suggest that an altered balance of signaling through 5-HT1A and 5-HT2A/C receptors in early life influences anxiety behavior.
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors: Ambalika
authors: A
authors: Sarkar
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.
authors: Parul
authors: P
authors: Chachra
authors: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India. Electronic address: vvaidya@tifr.res.in.
authors: Vidita A
authors: VA
authors: Vaidya
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D003863:Depression / Q000139:chemically induced / Q000503:physiopathology; D005473:Fluoxetine / Q000633:toxicity; D015870:Gene Expression; D008297:Male; D009043:Motor Activity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity
chemical_list: D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D017367:Selective Serotonin Reuptake Inhibitors
keywords: 5-HT(1A); 5-HT(2A); 5-HT(2C); Antidepressant; DOI; Prozac; SSRI; WAY-100635; ketanserin