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Open-field behavioural alterations in liver-impaired and sham-operated rats after acute exposure to the antidepressant venlafaxine
- Source :
- Basicclinical pharmacologytoxicology. 97(3)
- Publication Year :
- 2005
-
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.
- Subjects :
- Male
medicine.medical_specialty
medicine.medical_treatment
Venlafaxine
Toxicology
Open field
Rats, Sprague-Dawley
Pharmacokinetics
Internal medicine
medicine
Animals
Saline
Pharmacology
Behavior, Animal
business.industry
Portacaval Shunt, Surgical
Body Weight
Venlafaxine Hydrochloride
Brain
General Medicine
Organ Size
Cyclohexanols
Rats
Endocrinology
Liver
Anesthesia
Pharmacodynamics
Toxicity
Antidepressant
Antidepressive Agents, Second-Generation
Reuptake inhibitor
business
Locomotion
Selective Serotonin Reuptake Inhibitors
medicine.drug
Subjects
Details
- ISSN :
- 17427835
- Volume :
- 97
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Basicclinical pharmacologytoxicology
- Accession number :
- edsair.doi.dedup.....be900cf779f5370f29e21a98d98c6f10