Effects of Ca1 Glutamatergic Systems Upon Memory Impairments in Cholestatic Rats Publisher Pubmed



Hosseini N¹ ; Nasehi M² ; Radahmadi M³ ; Zarrindast MR^{1, 4, 5, 6} Show Affiliations
Source: Behavioural Brain Research Published:2013

Abstract

Background: Bile 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. Method: Cholestasis 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. Results: our 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. Conclusion: Our findings suggest the potential involvement of CA1 glutamatergic system(s) in cholestasis-induced memory deficits. © 2013 Elsevier B.V.