MiR‐33‐5p‐opioidergic Signaling Regulates Cognitive Impairment Induced by Bile Duct Ligation in Rats: Ameliorative Role of Naloxone

Objective The present study investigated the involvement of miR‐33‐5p‐opioidergic signaling in the regulation of cognitive impairment induced by bile duct ligation (BDL) in rats, with an emphasis on the ameliorative role of naloxone. Methods Among the four groups of Wistar rats (control, sham, BDL, and BDL + Naloxone [Nalx]), the common bile duct was occluded only in the BDL groups. Fourteen days after BDL induction and following completion of the analysis of the liver function tests of alkaline phosphatase, alanine aminotransferase, aspartate transaminase, direct bilirubin, total bilirubin, gamma‐glutamyl transpeptidase (GGT), and lactate dehydrogenase, the cognitive tests and electrophysiological field potential responses were recorded. Then, the hippocampus was assessed for the expression level of miR‐33‐5p using PCR. Ultimately, a histopathological study of the liver and hippocampus was carried out. Results The findings revealed that except for GGT ( p = 0.1935), all liver function tests were elevated ( P = 0.0001) following BDL. The impaired inhibitory avoidance memory ( P < 0.0001) and plasticity ( P < 0.0001) and the hippocampal overexpression of miR‐33‐5p following BDL ( P <0.0001) were ameliorated by Nalx. In a qualitative histopathological study of the liver and hippocampus, Nalx attenuated the BDL‐induced changes. Conclusions It is concluded that the BDL‐mediated dysfunction has a molecular, electrophysiological, and histopathological basis and might be regulated via miR‐33‐5p and opioidergic signaling. The study emphasizes the potential ameliorative role of Nalx on biliary and nervous system pathologies.