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

Kugelberg, Fredrik C.; Apelqvist, Gustav; Carlsson, Bjorn; Ahlner, Johan and Bengtsson, Finn LU (2006) In Basic & Clinical Pharmacology & Toxicology2004-01-01+01:002014-01-01+01:00 99(1). p.80-88
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... (More)
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. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Basic & Clinical Pharmacology & Toxicology2004-01-01+01:002014-01-01+01:00
volume
99
issue
1
pages
80 - 88
publisher
Wiley-Blackwell
external identifiers
  • wos:000238892700013
  • scopus:33745815170
ISSN
1742-7843
DOI
10.1111/j.1742-7843.2006.pto_449.x
language
English
LU publication?
yes
id
d93fe095-ce9e-4a82-b903-5245dfe72a31 (old id 404231)
date added to LUP
2007-10-08 09:06:36
date last changed
2019-02-20 04:02:43
@article{d93fe095-ce9e-4a82-b903-5245dfe72a31,
  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.},
  author       = {Kugelberg, Fredrik C. and Apelqvist, Gustav and Carlsson, Bjorn and Ahlner, Johan and Bengtsson, Finn},
  issn         = {1742-7843},
  language     = {eng},
  number       = {1},
  pages        = {80--88},
  publisher    = {Wiley-Blackwell},
  series       = {Basic & Clinical Pharmacology & Toxicology2004-01-01+01:002014-01-01+01:00},
  title        = {Sustained citalopram treatment in experimental hepatic encephalopathy: Effects on entrainment to the light-dark cycle and melatonin},
  url          = {http://dx.doi.org/10.1111/j.1742-7843.2006.pto_449.x},
  volume       = {99},
  year         = {2006},
}