Delay in the recovery of normal sleep-wake cycle after disruption of the light-dark cycle in mice: a bipolar disorder-prone animal model?
OBJECTIVE
Disruption of the circadian rhythm is known as a provoking factor for manic episodes. Individual differences exist in the recovery rate from disruption in the general population. To develop a screening method to detect individuals vulnerable to bipolar disorder, the authors observed the relationship between the recovery of the normal sleep-wake cycle after switching the light-dark (LD) cycle and quinpirole-induced hyperactivity in mice.


METHODS
Sixteen male mice (age of 5 weeks, weight 28-29 gm) were subjected to a circadian rhythm disruption protocol. Sleep-wake behaviors were checked every 5 min for a total duration of 15 days, i.e., 2 days of baseline observations, 3 days of LD cycle changes, and 10 days of recovery. During the dark cycle on the 16th experimental day, their general locomotor activities were measured in an open field for 120 minutes after an injection of quinpirole (0.5 mg/kg, s.c.).


RESULTS
The individual differences in the recovery rate of the baseline sleep-wake cycle were noted after 3 days of switching the LD cycle. Fifty percent (n=8) of the mice returned to the baseline cycle within 6 days after normalizing the LD cycle (early recovery group). The locomotor activities of mice that failed to recover within 6 days (delayed recovery group) were significantly higher (mean rank=12.25) than those of the early recovery group (mean rank=4.75, u=62.0, p=0.001, Mann-Whitney U test).


CONCLUSIONS
Given that the quinpirole-induced hyperactivity is an animal model of bipolar disorder, our results suggest individuals who have difficulties in recovery from circadian rhythm disruption may be vulnerable to bipolar disorder.
Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea.
Sun Hwa
SH
Jung
Department of Psychiatry, Pusan National University School of Medicine, Busan, Republic of Korea.
Je-Min
JM
Park
Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea.
Eunsoo
E
Moon
Department of Psychiatry, Pusan National University School of Medicine, Busan, Republic of Korea.
Young In
YI
Chung
Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea.
Byung Dae
BD
Lee
Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea.
Young Min
YM
Lee
Department of Psychiatry, Pusan National University School of Medicine, Busan, Republic of Korea.
Ji Hoon
JH
Kim
Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea.
Soo Yeon
SY
Kim
Department of Psychiatry, Pusan National University Hospital, Busan, Republic of Korea.
Hee Jeong
HJ
Jeong
Animal model; Bipolar disorder; Circadian rhythm; Locomotor activity; Open field test; Quinpirole