Effects of ketamine on spatial learning and memory behaviour and expression of ChAT in hippocampus of aged rats

Objective:To study the effects of administering anesthetic ketamine on the spatial learning and memory behavior and the expression of ChAT in hippocampus of aged rats. Methods: 48 aged male SD rats were randomly divided into 4 groups(n=12): 1 week control group(C1), 1 week ketamine group(K1), 3 week control group(C3), 3 week ketamine group(K3). Ketamine groups(K1 and K3) received the anesthetic with an initial dose of 80 mg/kg by intraperitoneal injection. Half of the initial dose were administered in every other 15min with 3 times in all. The control groups(C1 and C3)were given equal volume of 0.9% saline intraperitoneally. After testing the ability of learning and spatial localization for C1 and K1 groups by Morris water maze(MWM), the rats were anesthetized for removing the hippocampus while being infused. HE staining and immunocytochemistry were used to examine hippocampus neurons and ChAT positive cells. Results: ①MWM: At day 1 to day 4, the escape latency in K1 group was observed significantly longer compared with C1 group(P0.05 or P0.01), but at day 5 and 6, there was no difference(P0.05), and the time consumption across the original platform in the spatial probe test in K1 group was less than C1 group (P0.05). ②Immunocytochemistry: In K1 group, ChAT positive cells was less than that of C1 group(P0.05), but there was no significantly difference between group K3 and group C3 (P0.05).③HE assay: Electronic microscopy showed no abnormal changes of hippocampal neurons in two groups. Conclusion: When ketamine is administered in aged rats to the clinical dosage, it can affect the spatial learning and memory behavior. The impairment may be reversed with advance of time, which suggests that the mechanism of this damage might be related to the change of ChAT positive cells.