title: Differences in Anxiety-Like Behavior within a Batch of Wistar Rats Are Associated with Differences in Serotonergic Transmission, Enhanced by Acute SRI Administration, and Abolished By Serotonin Depletion.
abstract: BACKGROUND
  The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxiety-enhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxiety-prone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission.
  
  
  METHODS
  The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs.
  
  
  RESULTS
  "Anxious" rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in "anxious" but not "non-anxious" rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in "anxious" but not "non-anxious" rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram.
  
  
  CONCLUSIONS
  Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson).
authors.forename: Jakob
authors.initials: J
authors.lastname: Näslund
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson).
authors.forename: Erik
authors.initials: E
authors.lastname: Studer
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson).
authors.forename: Robert
authors.initials: R
authors.lastname: Pettersson
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson).
authors.forename: Melker
authors.initials: M
authors.lastname: Hagsäter
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson).
authors.forename: Staffan
authors.initials: S
authors.lastname: Nilsson
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson).
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden (Dr Näslund, Mr Studer, Mr Pettersson, Drs Hagsäter, Nissbrandt, and Eriksson); Institute of Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden (Dr Nilsson). elias.eriksson@neuro.gu.se.
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D010134:Fenclonine / Q000494:pharmacology; D007206:Individuality; D008297:Male; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D015283:Citalopram; D010134:Fenclonine; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase; C504569:tph2 protein, rat
keywords: Serotonin; anxiety; elevated plus maze; serotonin reuptake inhibitors; tryptophan hydroxylase 2