title: Transient anorexia, hyper-nociception and cognitive impairment in early adjuvant arthritis in rats.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is associated with enhanced pro-inflammatory cytokine levels, pain, anorexia, and cognitive changes. The enhanced production of cytokines appears before the full manifestation of the disease. So far, any experimental data on behavioral effects of early arthritis are lacking. In the present series we describe anorexia early changes in, pain hyper-sensitivity and altered cognitive behavior during the first four days of adjuvant arthritis in rats (AA), when no clinical signs are yet apparent.
  
  
  METHODS
  AA was induced to male Lewis rats by a single injection of complete Freund's adjuvant (cFA) at the base of the tail. Plasma leptin and ghrelin were measured using specific RIA methods. Gene expressions for food-regulatory peptides, neuropeptide-Y (NPY) and interleukin-1β (IL-1β) in the hypothalamic arcuate nuclei (nARC), were quantitated by TaqMan real-time PCR. Pain sensation was measured on all four limbs and tail by the plantar test. Cognitive functions were tested in the Morris water maze (MWM).
  
  
  RESULTS
  Levels of orexigenic ghrelin as well as mRNA expression of orexigenic NPY in nucleus arcuatus (nRC)re significantly enhanced on day 2 of AA only. Reduced body weight and food intake persisted by day 4 with the most profound reduction on day 2. The mRNA for anorexigenic IL-1β in the nARC was significantly enhanced on days 2 and 4. Enhanced pain sensitivity was observed on day 2, as was the cognitive impairment given by longer time to find the hidden platform, longer time spent in thigmotaxis zone, and longer trajectory. The less effective strategy used to find the hidden platform was observed up to the day 4 of AA.
  
  
  CONCLUSIONS
  Early stage of AA brings about reduced body weight, food intake, and activation of central orexigenic pathways. The observed anorexia could be ascribed to the over-expression of anorexigenic IL-1β which dominates over the NPY orexigenic effects. On day 2 of AA higher pain sensitivity and cognitive impairment appear. All the observed change tend to recover by day 4 of the disease.
authors.affiliation: Department of Normal, Pathological and Clinical Physiology, Third Faculty of Medicine, Charles University in Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Skurlova
authors.forename: A
authors.initials: A
authors.lastname: Stofkova
authors.forename: A
authors.initials: A
authors.lastname: Kiss
authors.forename: J
authors.initials: J
authors.lastname: Belacek
authors.forename: O
authors.initials: O
authors.lastname: Pecha
authors.forename: K
authors.initials: K
authors.lastname: Deykun
authors.forename: J
authors.initials: J
authors.lastname: Jurcovicova
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000737:chemistry; D001169:Arthritis, Experimental / Q000150:complications* / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology*; D015870:Gene Expression; D054439:Ghrelin / Q000097:blood; D006930:Hyperalgesia / Q000209:etiology*; D053583:Interleukin-1beta / Q000235:genetics; D020738:Leptin / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013997:Time Factors
chemical_list: D054439:Ghrelin; D053583:Interleukin-1beta; D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger