title: Altered brain activation pattern associated with drug-induced attenuation of enhanced depression-like behavior in rats bred for high anxiety.
abstract: BACKGROUND
  The enhanced depression-like behavior in the forced swim test displayed by rats selectively bred for high anxiety-related behavior (HAB) as compared with their low anxiety counterparts (LAB) is abolished by chronic paroxetine treatment. The aim of the present study was to identify neuronal substrates underlying this treatment response in HABs.
  
  
  METHODS
  The HAB rats received paroxetine (10 mg/kg/day) for 24 days via drinking water, and drug-induced modulation of neuronal activation patterns in response to forced swimming was mapped with the expression of the immediate early gene c-Fos as marker.
  
  
  RESULTS
  Chronic paroxetine treatment reduced the immobility scores during forced swimming, confirming the previously observed antidepressant-like effect in these animals, and attenuated the forced swim-induced c-Fos response in a restricted set (11 of 70) of brain areas. These included limbic areas such as the prelimbic cortex, parts of the amygdala, the bed nucleus of the stria terminalis, dorsal hippocampus, dorsal lateral septum as well as hypothalamic and hindbrain areas (dorsolateral periaqueductal gray [PAG], locus coeruleus). Untreated LAB rats, which displayed low depression-like behavior comparable to that of treated HABs, also showed low swim stress-induced c-Fos response in most of these same areas, further supporting an association of attenuated neuronal excitability in the identified areas with attenuated depression-like behavior.
  
  
  CONCLUSIONS
  These findings indicate that modulation of neuronal activation in a restricted set of defined, mainly limbic as well as selected hypothalamic and hindbrain areas by paroxetine treatment is associated with the reduction of enhanced depression-like behavior in a psychopathological animal model.
authors.affiliation: Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria.
authors.forename: Patrik
authors.initials: P
authors.lastname: Muigg
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hoelzl
authors.forename: Klara
authors.initials: K
authors.lastname: Palfrader
authors.forename: Inga
authors.initials: I
authors.lastname: Neumann
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wigger
authors.forename: Rainer
authors.initials: R
authors.lastname: Landgraf
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003863:Depression / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D017374:Paroxetine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016760:Proto-Oncogene Proteins c-fos; D017374:Paroxetine