title: Chronic oral carbamazepine treatment elicits mood-stabilising effects in mice.
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.
authors.affiliation: 1 School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel.
authors.forename: Nirit Z
authors.initials: NZ
authors.lastname: Kara
authors.affiliation: 2 Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Karpel
authors.affiliation: 2 Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Toker
authors.affiliation: 2 Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
authors.forename: Galila
authors.initials: G
authors.lastname: Agam
authors.affiliation: 3 Department of Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beersheba, Israel.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Belmaker
authors.affiliation: 1 School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Einat
mesh_terms: D000284:Administration, Oral; D000339:Affect / Q000187:drug effects*; D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy; D002220:Carbamazepine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009043:Motor Activity
chemical_list: D002220:Carbamazepine