Is anorexia in thioacetamide-induced cirrhosis related to an altered brain serotonin concentration?

Pol J Pharmacol. 2004 Jan-Feb;56(1):73-8.

Abstract

Anorexia or loss of appetite, one of the most typical symptoms observed in experimental and human cirrhosis, has been proposed to be associated with altered brain serotonin (5-HT) metabolism. In order to evaluate this hypothesis, brain 5-HT, its precursor tryptophan (TRP) and its metabolite 5-hydroxyindole-acetic acid (5-HIAA) were measured in brains of rats with thioacetamide (TAA)-induced liver cirrhosis. Thioacetamide at a dose of 500 mg/l in drinking water was administered for 6 weeks and during this period food intake was carefully measured in order to monitor the loss of appetite or decrease in food intake observed in cirrhosis. Concentrations of brain TRP, 5-HT and 5-HIAA were measured by HPLC with electrochemical detection. In TAA-treated rats, concentrations of 5-HT, TRP and 5-HIAA were increased in brain (44%, 33% and 36% of controls, p < 0.01). In plasma and liver of cirrhotic rats, TRP levels were increased (195% and 43%; p < 0.01). Plasma glucose and albumin levels were decreased (50%; p < 0.01 and 31%). Food intake, growth rate and locomotor activity of TAA-treated rats also decreased (73%, 22% and 73% of controls; p < 0.01). The results of this study show that brain 5-HT concentration in rats is increased in TAA-treated rats and it may, therefore, play an important role in the pathogenesis of anorexia associated with TAA-induced cirrhosis.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Anorexia / chemically induced
  • Anorexia / complications*
  • Behavior, Animal
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Brain Chemistry / drug effects*
  • Disease Models, Animal
  • Drinking
  • Drug Administration Schedule
  • Eating / drug effects
  • Exploratory Behavior / drug effects
  • Female
  • Fibrosis / chemically induced*
  • Fibrosis / complications*
  • Hydroxyindoleacetic Acid / chemistry
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / physiopathology
  • Motor Activity / drug effects
  • Pakistan
  • Rats
  • Rats, Wistar
  • Serotonin / chemistry*
  • Serotonin / metabolism
  • Serum Albumin / chemistry
  • Serum Albumin / drug effects
  • Thioacetamide / administration & dosage
  • Thioacetamide / adverse effects*
  • Time Factors
  • Tryptophan / blood

Substances

  • Blood Glucose
  • Serum Albumin
  • Thioacetamide
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Tryptophan