Background: Mice with a deletion at exon 19 of the circadian locomotor output cycles Kaput gene (Clock delta19) exhibit mania-like behavior and have been one of the most common animal models for bipolar disorder (BD). The predictive validity of the Clock delta19 was investigated via studies using lithium previously. Determination of effects of other mood stabilizers on Clock delta19 mouse would be helpful for better understanding of the mechanism underlined.
Methods: Wildtype (WT) and Clock delta19 mice were treated with saline (n = 10 for WT and n=10 for Clock delta19) or valproate (VPA) (n = 10 for WT and n=10 for Clock delta19) 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 Clock delta19 mouse (n = 8 for each) were also determined.
Results: VPA can reverse hyperactivity, lower level of anxiety-like and depression-like behaviors of the Clock delta19 mouse. Clock delta19 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 Clock delta19 mouse.
Conclusion: Our results indicated that chronic VPA treatment can reverse the mania-like behaviors of the Clock delta19 mouse and further consolidate the validity of the Clock delta19 mouse as a model of BD. Monoamine neurotransmitters and their metabolites in the hippocampus are partly regulated by mutation of the Clock gene or VPA treatment.
Keywords: Clockdelta19 mouse; bipolar disorder; mania-like behavior; neurotransmitter; valproate.
© 2021 Liu et al.