Portal hypertension in 18-month-old rats: memory deficits and brain metabolic activity

Portal hypertension is a major complication of cirrhosis that frequently leads to a neuropsychiatric disorder that affects cognition. We compared the performance of 18-month-old prehepatic portal hypertensive rats (PH) and 18-month-old normal rats (CO) in spatial short-term and reference memory tasks in the Morris water maze and in active avoidance task. The PH group showed worse spatial short-term memory than the CO group. Also, the PH group tended to perform worse than the CO group in the reference memory task, but it presented a correct acquisition of the active avoidance task. We assessed the brain metabolic activity of the animals by means of cytochrome c-oxidase (COx) histochemistry. We found that the PH group developed prefrontal dysfunction characterized by increased COx activity in this region compared to the CO group. Similar results were found in the medial mammillary nucleus and dentate gyrus, whereas the CA1 area, bed nucleus of the stria terminalis, and supramammillary nucleus showed lower COx activity in the PH group as compared to the CO group. We conclude that the 18-month-old portal hypertensive rats present spatial memory impairment without alteration of implicit learning. This deficit could be related to the alteration of the metabolic activity of the brain regions involved in the processing of spatial memories.