Sustained citalopram treatment in experimental hepatic encephalopathy: Effects on entrainment to the light-dark cycle and melatonin

Research output: Contribution to journalArticle

Abstract

Patients with chronic hepatic encephalopathy often display altered diurnal rhythm as well as other affective disturbances which motivate treatment with antidepressants. We investigated the effects of sustained treatment with citalopram (10 mg/kg daily, 10 days) on 24-hr behavioural open-field activities in portacaval-shunted (PCS) rats and sham-operated control rats. In addition, the daytime and nighttime serum melatonin levels, as well as the serum concentrations of the enantiomers of citalopram and its metabolites, were analyzed. Untreated PCS rats showed reduced locomotor and rearing activities during nighttime. Citalopram treatment resulted in elevated behavioural activity in the PCS rats during night, indicative of an improved entrainment to the light-dark cycle, whereas no behavioural effect could be observed in sham rats. Higher melatonin levels in both PCS and sham rats were observed during nighttime compared with daytime, but the untreated PCS rats also showed higher daytime melatonin level than the corresponding sham group. Citalopram treatment seemed not to have any major effect on the melatonin levels. Higher serum levels of both citalopram and metabolites were observed in PCS rats as compared to sham rats. An altered ratio between the S- and R-enantiomers could also be observed in the PCS rats. In conclusion, the present data support the contention of a disturbed diurnal rhythm, and that the melatonin activity may be altered, in chronic hepatic encephalopathy. The citalopram treatment resulted in similar behavioural performances and daytime serum melatonin levels in PCS rats and controls, although pharmacokinetic differences were present between the groups.

Details

Authors
  • Fredrik C. Kugelberg
  • Gustav Apelqvist
  • Bjorn Carlsson
  • Johan Ahlner
  • Finn Bengtsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology
Original languageEnglish
Pages (from-to)80-88
JournalBasic & Clinical Pharmacology & Toxicology
Volume99
Issue number1
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes