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Chronic oral carbamazepine treatment elicits mood-stabilising effects in mice

Published online by Cambridge University Press:  29 May 2013

Nirit Z. Kara ,
Orit Karpel ,
Lilach Toker ,
Galila Agam ,
Robert H. Belmaker  and
Haim Einat
Nirit Z. Kara
Affiliation:
School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
Orit Karpel
Affiliation:
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
Lilach Toker
Affiliation:
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
Galila Agam
Affiliation:
Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel Department of Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
Robert H. Belmaker
Affiliation:
Department of Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel
Haim Einat*
Affiliation:
School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel College of Pharmacy, University of Minnesota, Minneapolis, MN, USA
*
Haim Einat, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, 2 Rabenu Yeruham St., Tel-Aviv, Israel. Tel: (972)3-680-2536; Fax: (972)3-680-2526; E-mail: haimh@mta.ac.il
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Abstract

Objective

The underlying biology of bipolar disorder and the mechanisms by which effective medications induce their therapeutic effects are not clear. Appropriate use of animal models are essential to further understand biological mechanisms of disease and treatment, and further understanding the therapeutic mechanism of mood stabilisers requires that clinically relevant administration will be effective in animal models. The clinical regimens for mood-stabilising drugs include chronic oral administration; however, much of the work with animal models includes acute administration via injection. An effective chronic and oral administration of the prototypic mood stabiliser lithium was already established and the present study was designed to do the same for the mood stabiliser carbamazepine.

Methods

Mice were treated for 3 weeks with carbamazepine in food. ICR mice were treated with 0.25%, 0.5% and 0.75%, and C57bl/6 mice with 0.5% and 0.75%, carbamazepine in food (w/w, namely, 2.5, 5.0 or 7.5 g/kg food). Mice were then tested for spontaneous activity, forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperactivity.

Results

Oral carbamazepine administration resulted in dose-dependent blood levels reaching 3.65 μg/ml at the highest dose. In ICR mice, carbamazepine at the 0.5% dose had no effect on spontaneous activity, but significantly reduced immobility in the TST by 27% and amphetamine-induced hyperactivity by 28%. In C57bl/6 mice, carbamazepine at the 0.75% dose reduced immobility time in the FST by 26%.

Conclusions

These results demonstrate a behaviourally effective oral and chronic regimen for carbamazepine with mood stabilising-like activity in a standard model for mania-like behaviour and two standard models for depression-like behaviour.

Keywords

animal modelsanticonvulsantsbipolar disorderdepressionmaniamicemood-stabilisers
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 1 , February 2014 , pp. 29 - 34
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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