Introduction: Increases in endogenous opioids resulting in itching and nociception have been reported in cholestasis. N-Methyl-D-Aspartate (NMDA) receptors are involved in nociception, and we hypothesized NMDA receptors to be affected in cholestasis. The aim of this study was to evaluate gene expression of main subunit of NMDA receptors (NR1) in the prefrontal cortex, the hippocampus, and the striatum in cholestatic rats. Materials and methods: We used male Wistar rats weighing 300 ±20 g. Three experimental groups including control, sham operated group with laparotomy but no bile duct ligation (BDL), and cholestatic group with laparotomy and BDL were used. After 21 days of laparotomy or BDL, rats were sacrificed, serum levels of bilirubin and blood urea nitrogen (BUN), and also liver weight to body weight ratio were examined. In addition, the whole brain quickly removed from the skull, and the prefrontal cortex (PFC), hippocampus and striatum were immediately dissected on an ice-chilled sterile surface. A semi-quantitative RT-PCR method was used for evaluating gene expression. Results: The results showed a significant increase of serum levels of bilirubin, BUN and liver weight to body weight ratio in the cholestatic group compared to sham group; confirming induction of cholestasis. The mRNA levels of NR1 in cholestatic group significantly decreased in the PFC, significantly increased in the hippocampus, but no significant change was observed in the striatum compared to sham group. It can be concluded that cholestasis causes changes in the expression of NMDA receptors in some areas of the brain could affect sensory perception, which in turn result in sensory and psychological disorders during cholestasis.
