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Open-field behavioural alterations in liver-impaired and sham-operated rats after acute exposure to the antidepressant venlafaxine

Kugelberg, FC; Apelqvist, G; Wikell, Cecilia LU and Bengtsson, F (2005) In Basic & Clinical Pharmacology & Toxicology 97(3). p.155-161
Abstract
Patients with chronic liver impairment often display symptoms of affective psychiatric nature where the choice for antidepressant treatment is rational. Since caution is recommended when these drugs are used in such patients, a dose reduction is usually performed. We have previously reported that a dose reduction to liver-impaired portacaval shunted rats has resulted in similar brain concentrations of venlafaxine as compared to sham-operated control rats that received a two times higher dose. The main aim of the present study was therefore to investigate if this "normalisation" in pharmacokinetics of the portacaval-shunted rats also was true for the pharmacodynamic response in terms of drug effect on spontaneous open-field behaviour. Thus,... (More)
Patients with chronic liver impairment often display symptoms of affective psychiatric nature where the choice for antidepressant treatment is rational. Since caution is recommended when these drugs are used in such patients, a dose reduction is usually performed. We have previously reported that a dose reduction to liver-impaired portacaval shunted rats has resulted in similar brain concentrations of venlafaxine as compared to sham-operated control rats that received a two times higher dose. The main aim of the present study was therefore to investigate if this "normalisation" in pharmacokinetics of the portacaval-shunted rats also was true for the pharmacodynamic response in terms of drug effect on spontaneous open-field behaviour. Thus, portacaval-shunted rats received a single reduced dose (5 mg/kg) of venlafaxine or saline, whereas sham-operated rats received either 10 mg/kg or saline. Thereafter, central and peripheral arena locomotor and rearing activities were recorded during 60 min. The venlafaxine-treated portacaval-shunted and sham rats displayed reduced and unchanged overall behavioural activities compared with corresponding controls, respectively. However, the ratios between centrally and peripherally performed behavioural activities were higher in the venlafaxine-treated sham rats, indicating an increase in central arena activity as compared to the sham-saline and portacaval-shunted rats. The present study indicates that, despite a 50% dose reduction, caution still is necessary when antidepressants are used in liver insufficient subjects. This study also shows the importance of detailed open-field behavioural studies in which both central and peripheral activities are recorded for measurement of open-field behavioural drug effects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Basic & Clinical Pharmacology & Toxicology
volume
97
issue
3
pages
155 - 161
publisher
Wiley-Blackwell
external identifiers
  • pmid:16128909
  • wos:000231906800005
  • scopus:24744444721
ISSN
1742-7843
DOI
10.1111/j.1742-7843.2005.pto_97385.x
language
English
LU publication?
yes
id
a40af052-5626-4fdf-80c1-40f95a9e6501 (old id 224651)
date added to LUP
2007-08-21 08:08:16
date last changed
2017-11-05 03:44:36
@article{a40af052-5626-4fdf-80c1-40f95a9e6501,
  abstract     = {Patients with chronic liver impairment often display symptoms of affective psychiatric nature where the choice for antidepressant treatment is rational. Since caution is recommended when these drugs are used in such patients, a dose reduction is usually performed. We have previously reported that a dose reduction to liver-impaired portacaval shunted rats has resulted in similar brain concentrations of venlafaxine as compared to sham-operated control rats that received a two times higher dose. The main aim of the present study was therefore to investigate if this "normalisation" in pharmacokinetics of the portacaval-shunted rats also was true for the pharmacodynamic response in terms of drug effect on spontaneous open-field behaviour. Thus, portacaval-shunted rats received a single reduced dose (5 mg/kg) of venlafaxine or saline, whereas sham-operated rats received either 10 mg/kg or saline. Thereafter, central and peripheral arena locomotor and rearing activities were recorded during 60 min. The venlafaxine-treated portacaval-shunted and sham rats displayed reduced and unchanged overall behavioural activities compared with corresponding controls, respectively. However, the ratios between centrally and peripherally performed behavioural activities were higher in the venlafaxine-treated sham rats, indicating an increase in central arena activity as compared to the sham-saline and portacaval-shunted rats. The present study indicates that, despite a 50% dose reduction, caution still is necessary when antidepressants are used in liver insufficient subjects. This study also shows the importance of detailed open-field behavioural studies in which both central and peripheral activities are recorded for measurement of open-field behavioural drug effects.},
  author       = {Kugelberg, FC and Apelqvist, G and Wikell, Cecilia and Bengtsson, F},
  issn         = {1742-7843},
  language     = {eng},
  number       = {3},
  pages        = {155--161},
  publisher    = {Wiley-Blackwell},
  series       = {Basic & Clinical Pharmacology & Toxicology},
  title        = {Open-field behavioural alterations in liver-impaired and sham-operated rats after acute exposure to the antidepressant venlafaxine},
  url          = {http://dx.doi.org/10.1111/j.1742-7843.2005.pto_97385.x},
  volume       = {97},
  year         = {2005},
}