Effects of CA1 glutamatergic systems upon memory impairments in cholestatic rats.
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.


METHODS
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.


CONCLUSIONS
Our findings suggest the potential involvement of CA1 glutamatergic system(s) in cholestasis-induced memory deficits.
Institute for Cognitive Science Studies (ICSS) , Tehran, Iran.
Nasrin
N
Hosseini
Mohammad
M
Nasehi
Maryam
M
Radahmadi
Mohammad-Reza
MR
Zarrindast
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D002779:Cholestasis / Q000150:complications*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid
Cholestasis; D-AP7; NMDA; Rat; Step-through passive avoidance test