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Effects of chronic citalopram treatment on central and peripheral spontaneous open-field behaviours in rats
Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
Department of Clinical Pharmacology, Institute of Laboratory Medicine,Lund University, Lund, Sweden.
Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Linköpings universitet, Hälsouniversitetet.
2002 (engelsk)Inngår i: Pharmacology and Toxicology, ISSN 0901-9928, E-ISSN 1600-0773, Vol. 90, nr 6, s. 303-310Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The spontaneous open-field behavioural effects of 10 days of chronic treatment with two clinical doses (10 and 20 mg/kg daily) and one high/toxic dose (100 mg/kg daily) of the selective serotonin reuptake inhibitor citalopram (delivered subcutaneously by implanted osmotic pumps) were examined in rats. Central and peripheral arena locomotor and rearing activities were recorded simultaneously, and the data were assessed during the first hour as well as during the following 24 hr (the latter for effects on the diurnal rhythm). Rats treated with 100 mg/kg daily exhibited lower peripheral locomotor and rearing activities than the other groups during the first test hour. The ratio between central and peripheral activity increased in a dose-dependent non-proportional manner during the first test hour, indicating a general increase in the central arena activity exerted by the rats when treated with citalopram. No major differences were observed between any of the four groups in overall behavioural activities over the 24-hr period. This study indicated that the open-field locomotor and rearing behaviours in normal rats were affected by increasing doses of racemic citalopram, particularly during the first hour of adaptation.

sted, utgiver, år, opplag, sider
2002. Vol. 90, nr 6, s. 303-310
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-27659DOI: 10.1034/j.1600-0773.2002.900603.xLokal ID: 12397OAI: oai:DiVA.org:liu-27659DiVA, id: diva2:248211
Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
Inngår i avhandling
1. Chiral and toxicological aspects of citalopram: an experimental study in rats
Åpne denne publikasjonen i ny fane eller vindu >>Chiral and toxicological aspects of citalopram: an experimental study in rats
2003 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Citalopram (CIT) is a selective serotonin reuptake inhibitor (SSRI), which is used for the treatment of different psychiatric disorders. The indications for prescription of OT are linked to high risks for intentional intoxications. CIT is one of the most commonly found drugs in Swedish forensic autopsy cases. CIT is a chiral compound, which exists as a racemic mixture (50:50) of the S-(+)-enantiomer (S-CIT) and the R-(-)-enantiomer (R-CIT). The main metabolites, demethylcitalopram (DCIT) and didemethylcitalopram (DCIT), are also chiral compounds. The SSRI effect of CIT is mediated by S-CIT. The routine toxicological screening is an achiral analysis, in which the total amount of the two enantiomers of CIT and metabolites are measured. An extended analysis of the disposition of the Sand R-enantiomers may provide additional information in interpreting forensic toxicological results. Hence, the blood and brain dispositions of the enantiomers of CIT, DCIT and DDCIT in vivo as well as postmortem were studied in an animal model, which also included studies of the behavioural activity.

Rats underwent systemic CIT exposure of clinically relevant and high/toxic doses, which were administered acute, chronic or acute-on-chronic. Samples from serum/blood and two brain regions (cortex and mesencephalon-pons) were collected for analysis of the concentrations of the enantiomers of CIT and metabolites using a chiral high performance liquid chromatography (HPLC) method. The open-field locomotor and rearing activities were examined after the chronic CIT exposure.

Following chronic CIT administration, R-CIT was present in an increased proportion compared with S-CIT when higher CIT concentration prevailed. Higher drug levels were observed in brain than in serum, and the drug levels between the two compartments correlated well. The rats treated with the high/toxic dose displayed lower behavioural activity during the first test hour as compared to controls and rats given clinically relevant doses. No major effects of CIT on the behavioural rhythm were observed. Shortly after the acute CIT administration, the ratio between S- and R-CIT was close to unity, whereas R-OT was found in higher amount than S-CIT at the end of the study period. The heart blood levels of CIT and metabolites increased postmortem in comparison with the levels observed antemortem after acute, chronic and acute-on-chronic administration. Irrespective of administered dose, the ratios between the S- and R-enantiomers of CIT and DCIT, as well as the CIT/DCIT ratios, were similar antemortem and postmortem.

Chiral analysis provided additional information regarding the different administration procedures as compared to achiral analysis. The stereoselective in vivo disposition of the enantiomers of CIT and metabolites was found similar in blood and brain. An equal degree of postmortem redistribution was also seen regarding the enantiomers of CIT and metabolites. These findings may facilitate and improve the interpretation of forensic toxicological results in humans.

sted, utgiver, år, opplag, sider
Linköping: Linköpings universitet, 2003. s. 83
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 826
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-27508 (URN)12164 (Lokal ID)91-7373-512-4 (ISBN)12164 (Arkivnummer)12164 (OAI)
Disputas
2003-07-01, Patologsalen, Hälsouniversitetet, Linköping, 13:00 (svensk)
Opponent
Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2012-10-17bibliografisk kontrollert

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