PORTACAVAL ANASTOMOSIS DISRUPTS CIRCADIAN LOCOMOTOR-ACTIVITY AND PINEAL MELATONIN RHYTHMS IN RATS

To determine whether hepatic encephalopathy may be associated with a disruption of circadian function, the circadian rhythms of locomotor activity and pineal melatonin content were examined in an animal model of complete portal-systemic shunting, rats with a portacaval anastomosis (PCA). The locomotor activity rhythm of all sham-operated animals entrained normally to a light/dark cycle and exhibited a normal free-running period during exposure to constant light. In constrast, PCA led to a dampening of the locomotor activity rhythm in all animals and the abolishment of a circadian periodicity in the activity rhythm of approximately 50% of rats during exposure to either a light/dark cycle or constant light. While normal diurnal variations of pineal melatonin content were seen in sham-operated rats, the amplitude of this variation appeared to be decreased in PCA animals. The similar effects of PCA on both a behavioral and an endocrine circadian rhythm, known to be regulated by a common neural pacemaker, coupled with studies indicating that a variety of other circadian rhythms may be disrupted in both animals and humans with hepatic dysfunction, suggests that this circadian disturbance originates within the pacemaker or on one of its afferent/efferent pathways.