Effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in developing rats

Objective To investigate the effect of 17β-estradiol on ketamine-induced long-term cognitive deficits in neonatal rats. Methods 80 SD male rats aged 7 days were randomly divided into group C, V, E, K and K+ E, and 16 per group. Group C was intraperitoneally injected with same volume of saline for three consecutive days, Group V was subcutaneously injected with same volume of sesame oil for three consecutive days, Group E was subcutaneously injected with 600 μg·kg-1 17β-estradiol for three consecutive days, group K was intraperitoneally injected with 75 mg·kg-1 ketamine for three consecutive days, group K+ E was intraperitoneally injected with 75 mg·kg-1 ketamine in combination with 600 μg·kg-1 17β-estradiol injected subcutaneously for three consecutive days. At 2 months of age, learning and memory abilities were tested with the Morris water maze. After Morris water maze test, ten rats from each group were decapitated and the prefrontal cortex (PFC) was isolated to detect acetylcholine esterase(AchE) activity with ELISA assay and to measure acetylcholine(Ach) level by hydroxylammonium chloride method. Results The escape latency ((40.26±2.36)s, (30.25±2.20)s, (21.55±2.42)s) and path length((1019.35±58.13)cm, (811.16±27.58)cm, (598.34±34.74)cm) of group K were more than those of group C on the third, fourth and fifth training days(all P<0.05), while escape latency ((29.46±2.20)s, (24.86±2.14)s, (17.20±1.91)s) and path length((913.90±41.89)cm, (729.42±31.36) cm, (487.64±18.61)cm) of group K+ E were significantly lower than those of group K(all P<0.05). On test day 6, rats were subjected to a probe trial, ratio of time spent in the target quadrant ((24.5±2.7)%) and the number of crossings over previous platform locations(1.9±0.5)in group K were fewer than those of group C (all P<0.05), while ratio of time spent in the target quadrant((42.3±3.0)%) and the number of crossings over previous platform locations(3.5±0.5)of group K+ E were more than those of group K (all P<0.05). The AchE activity((0.69±0.04)U·mg pro-1) in rats PFC of group K was significantly higher than that of group C ((0.52±0.06)U·mg pro-1) (P<0.05). The AchE activity of group K+ E ((0.58±0.12)U·mg pro-1) was lower than that of group K(P<0.05). The Ach level ((2.59±0.34)mg·g-1) in rats PFC of group K was significantly lower than that of group C ((4.35±0.56)mg·g-1)(P<0.05). The Ach level of group K+ E((3.88±0.61)mg·g-1) was higher than that of group K(P<0.05). Conclusions These results indicate that ketamine impairs learning and memory abilities as rat matures, while 17β-estradiol treatment improves these impairments by inhibiting AchE activity and increasing Ach level. Key words: 17β-estradiol; Ketamine; Prefrontal cortex; Morris water maze; Acetylcholine esterase; Acetylcholine