J Korean Neuropsychiatr Assoc.  2016 Aug;55(3):209-214. 10.4306/jknpa.2016.55.3.209.

Delay in Normalization of Disrupted Sleep-Wake Cycle in Mice as a Bipolar Disorder-Prone Animal Model (Bipolar Disorder-Prone Animal Model)

  • 1Department of Psychiatry, Pusan National University Hospital, Busan, Korea. jmback@pusan.ac.kr
  • 2Department of Psychiatry, Pusan National University School of Medicine, Yangsan, Korea.


This study was designed to test the hypothesis that delayed recovery from disrupted circadian rhythm is associated with both manic and depressive episodes in bipolar disorder.
Twenty-two male mice (age of five weeks, weight 28-30 gm) underwent three days of light-dark cycle disruption and 10 days of recovery phase. Sleep and wake state were checked every five minutes during the entire experimental period. After recovery phase, quinpirole (0.5 mg/kg, s.c.) was injected into the mice and open field locomotor activities were checked. Five days after the open field test, immobility time during the last 4 min in 6 min of forced swimming test was measured. Animals which recovered sleep-wake cycle within six days after light-dark cycle disruption were assigned to the early recovery group (n=14), and those that failed to recover in six days were assigned to the delayed recovery group (n=8). The locomotor activities and the immobility times of the two groups were compared by Mann-Whiney U test at two-tailed significance level of 0.05.
The locomotor activities of the delayed recovery group were higher (mean rank=16.19) than those of the early recovery group (mean rank=8.82, U=18.5, p=0.008). The immobility times did not differ by recovery time (U=32.0 p=0.110).
The results suggest that delayed recovery from circadian rhythm disruption raises the risk of manic symptoms rather than depressive symptoms.


Bipolar disorder; Circadian rhythm; Quinpirole; Open field test; Forced swimming test

MeSH Terms

Bipolar Disorder
Circadian Rhythm
Models, Animal*
Motor Activity
Physical Exertion


  • Fig. 1 Sleep-wake patterns observed by circadian rhythm disruption protocol.

  • Fig. 2 Locomotor activities in open field test after quinpirole injection.

  • Fig. 3 Immobility times of forced swim test. Immobility times of forced swim test between the early recovery group (mean rank=13.21) and the delayed recovery group (mean rank=8.50) were not different significantly (Mann-Whitney U test, U=32.0, p=0.110).


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