The effect of acute and chronic administration of naloxone on spatial memory in male cholestatic rats

Background and Objective: A great body of evidences suggested a marked elevation of endogenous opioid levels in plasma of animals with acute cholestasis. Endogenous opioids are implicated in the pathophysiology of cholestasis. Also, many studies have shown that endogenous opioids modulate memory processes. To clarify possible role of endogenous opioid receptors in information processing in acute cholestatic rats, we administered acute (5 mg/kg, i.p.) and chronic (by implanted osmotic mini-pump, s.c.) naloxone as an opioid receptor antagonist to male cholestatic rats. Materials and Methods: For this purpose, male rats were divided into eight groups. All the rats were assessed for spatial learning and memory (a major cognitive function in rats) by the Morris water maze task about 8 days after the first operation. Rats were subjected to 6 days of training in the Morris water maze (MWM): 4 days with the invisible platform to test spatial learning and on the 5th day, one day after the last trial, retention performance was examined in a single probe trial. On the 6th day, motivation and sensory-motor coordination was tested with the visible platform. Results: During the four consecutive acquisition trial days of this behavioral test, acute and chronic naloxone-treated bile duct-ligated rats had a significantly longer latency to escape than the bile duct-ligated groups (p Conclusion: The results of this study suggest that blockade of opioid receptors, both acute and chronic, results in spatial memory deficits in cholestatic rats.