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Open-field behavioural alterations in liver-impaired and sham-operated rats after acute exposure to the antidepressant venlafaxine
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
Klinisk farmakologi Lund.
Klinisk farmakologi Lund.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
2005 (English)In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, Vol. 97, no 3, 155-161 p.Article in journal (Refereed) Published
Abstract [en]

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 pharma-cokinetics 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. © Basic & Clinical Pharmacology & Toxicology 2005.

Place, publisher, year, edition, pages
2005. Vol. 97, no 3, 155-161 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-30904DOI: 10.1111/j.1742-7843.2005.pto_97385.xLocal ID: 16570OAI: diva2:251727
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2011-01-12

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Kugelberg, FredrikBengtsson, Finn
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