Research reportEffects of CA1 glutamatergic systems upon memory impairments in cholestatic rats

•Decrease in memory retrieval following cholestasis (11, 17 and 24 days post BDL).•Intra-CA1 injection of NMDA restored cholestasis-induced amnesia.•The previous effect was blocked by D-AP7.•D-AP7 potentiates the BDL-induced memory impairment but not significantly.

BackgroundBile duct ligation (BDL) is shown to induce cholestasis-related liver function impairments as well as consequent cognitive dysfunctions (i.e. impaired learning and memory formation). Glutamatergic neurotransmission plays an important role in hippocampal modulation of learning and memory function. The present study aimed to investigate the possible involvement of dorsal hippocampal (CA1) glutamatergic systems upon cholestasis-induced amnesia.MethodCholestasis was induced in male Wistar rats through double-ligation of the main bile duct (at two points) and transection of the interposed segment. Step-through passive avoidance test was employed to examine rats' learning and memory function. All drugs were injected into CA1 region of the hippocampus.Resultsour results indicated a decrease in memory retrieval following cholestasis (11, 17 and 24 days post BDL). Only subthreshold doses of N-methyl-d-aspartate (NMDA; 0.125 and 0.25 μg/μl) but not its effective dose (0.5 μg/μl), restored the cholestasis-induced amnesia in step-through passive avoidance test, 11, 17 and 24 days post BDL. This effect was blocked by the subthreshold dose of D-[1]-2-amino-7-phosphonoheptanoic acid (D-AP7, NMDA receptor antagonist; 0.0625 μg/μl, intra-CA1) at 0.125 μg/μl and 0.25 μg/μl doses of NMDA. Moreover, our data revealed that only effective doses of D-AP7 (0.125 and 0.25 μg/μl, intra-CA1) potentiate memory impairments in 11 days after BDL. It was noted that none of applied drugs/doses exerted an effect on memory acquisition and locomotors activity, 10 and 12 days post laparotomy, respectively.ConclusionOur findings suggest the potential involvement of CA1 glutamatergic system(s) in cholestasis-induced memory deficits.