Etomidate affects spatial learning and memory and neuronal apoptosis of rats via MAPK/ERK pathway

To observe the effect of etomidate on spatial learning and memory and neuronal apoptosis in rats of different ages.

The rats of different ages were divided into 3 age groups: juvenile (21-day old), adult (~3-months old) and elderly (~19-months old). Then, rats with similar age within a group were randomly divided into three subgroups, with 10 rats in each group. The experimental subgroups were intraperitoneally injected with etomidate (emulsion formulated, i.p. injection) at a dose of 5 mg/kg; the solvent control subgroups were given intraperitoneal injection of vehicle emulsion; and blank control subgroups received laparoscopic injection of normal saline. The rats' learning and memory ability was tested by Morris water maze. The tissue sections of each group's hippocampus were analyzed by H&E staining. The apoptosis of hippocampal cells was detected by TUNEL staining. MAPK expression in hippocampus was tested by Western blot.

Etomidate significantly extended the escape latency and reduced the platform crossings and the swimming time at original platform of juvenile rats, indicating that the spatial learning and memory function of juvenile rats can be affected by etomidate. However, etomidate had no effect on spatial learning and memory in adult and elderly rats. There were no obvious abnormalities in number of neurons and morphology of vertebral cells in the hippocampus of all experimental subgroups when compared with those of corresponding blank control subgroups. There was no statistically significant difference in apoptosis index of the hippocampal tissue between the experimental subgroups and corresponding blank control subgroups (P>0.05). Within juvenile group, the expression of p-ERK in the hippocampus of experimental subgroup was remarkably lower than that of solvent control subgroup and blank control subgroup (P<0.05), while there were no significant differences in p-p38 and p-JNK expressions among the three subgroups of juvenile rats (P>0.05). The expressions of p-ERK, p-p38 and p-JNK in adult and elderly rats were not affected by etomidate.

Etomidate may have certain effects on spatial learning and memory in juvenile rats but not in adult and elderly rats. Etomidate affects neither the number of neurons in the CA1 area of the hippocampus nor the morphology of vertebral cells and did not cause the apoptosis of nerve cells. The mechanism of etomidate influence on the spatial learning and memory function of young rats may connect with the inhibition of MAPK/ERK pathway.