Cognitive flexibility but not cognitive coordination is affected in rats with toxic liver failure.

Hepatic encephalopathy (HE), a consequence of liver damage, is associated with cognitive deficits. In this study, behavioral activity, non-associative learning, associative memory, cognitive coordination and flexibility were investigated in rats with subclinical HE evoked by thioacetamide treatment. Non-associative learning was studied in the open field (OF) set up in 12 HE and 8 saline-injected control rats (C). Memory was examined in spatial place avoidance tasks in 10 HE and 10 C rats. The Room+ Arena- task involved the selection of distal room stimuli from irrelevant arena stimuli (i.e. intramaze cues and/or self-motion information), which engages processes of cognitive coordination. Following the Room+ Arena- training, cognitive flexibility of rats was tested in the Arena+ place avoidance condition, which demands the previously ignored stimuli from arena. In the OF test HE and control rats behaved similar. They displayed high activity in the first block of each session and this pattern was stable. In both groups of rats darkness enhanced locomotor activity in comparison to light only in the first block. The HE and C rats avoided the to-be-avoided place in the Room+ Arena- task, whereas only HE rats were affected in the Arena+ task. In conclusion, these results demonstrate cognitive inflexibility in HE rats. We suggest that (1) the behavioral changes in the TAA model are typical of subclinical HE and (2) test for cognitive flexibility may be modified towards a routine use in patients with subclinical HE.