Valproate Reverses Mania-Like Behavior of Mouse and Alters Monoamine Neurotransmitters Metabolism in the Hippocampus.

BACKGROUND

Mice with a deletion at exon 19 of the circadian locomotor output cycles Kaput gene ( ) exhibit mania-like behavior and have been one of the most common animal models for bipolar disorder (BD). The predictive validity of the was investigated via studies using lithium previously. Determination of effects of other mood stabilizers on mouse would be helpful for better understanding of the mechanism underlined.

METHODS

Wildtype (WT) and mice were treated with saline (n = 10 for WT and n=10 for ) or valproate (VPA) (n = 10 for WT and n=10 for ) for 10 days. The hyperactivity, anxiety-like behaviors and depression-like behaviors were tested. The concentration of monoamine neurotransmitters and their metabolites in the hippocampus of saline or VPA treated WT and mouse (n = 8 for each) were also determined.

RESULTS

VPA can reverse hyperactivity, lower level of anxiety-like and depression-like behaviors of the mouse. mouse exhibited lower levels of serotonin (5-HT) and dopamine (DA) in right hippocampus compared to WT mouse. Chronic VPA treatment did not affect the levels of 5-HT and DA, but can reduce the level of levodopa (L-DOPA) in the right hippocampus of mouse.

CONCLUSION

Our results indicated that chronic VPA treatment can reverse the mania-like behaviors of the mouse and further consolidate the validity of the mouse as a model of BD. Monoamine neurotransmitters and their metabolites in the hippocampus are partly regulated by mutation of the gene or VPA treatment.