Role of GPR30 in reduction of ketamine-induced long-term cognitive dysfunction by 17β estradiol in neonatal rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of G protein-coupled receptor 30 (GPR30) in reduction of ketamine-induced long-term cognitive dysfunction by 17β estradiol in neonatal rats.Methods:Thirty healthy male Sprague-Dawley rats, aged 7 days, weighing 11-18 g, were divided into 5 groups ( n=6 each) using a random number table method: control group (group C), ketamine group (group K), 17β estradiol plus ketamine group (group KE), GPR30 agonist G1 plus ketamine group (group G1K) and GPR30 inhibitor G15 plus 17β estradiol plus ketamine group (group G15EK). Ketamine 75 mg/kg was intraperitoneally injected in group K. In group EK, 17β estradiol 600 μg/kg was subcutaneously injected, and ketamine 75 mg/kg was intraperitoneally injected.In group G1K, G1 200 μg/kg was subcutaneously injected, and ketamine 75 mg/kg was intraperitoneally injected.In group G15EK, G15 300 μg/kg and 17β estradiol 600 μg/kg were subcutaneously injected, and ketamine 75 mg/kg was intraperitoneally injected.The equal volume of normal saline was intraperitoneally given in group C. The injection was performed every 24 h for 3 consecutive days.All the rats were allowed to grow up till postnatal day 60, and then Morris water maze test was performed to evaluate their spatial learning and memory function.The rats were sacrificed after the end of Morris water maze test, and hippocampi were removed for determination of contents of acetyl cholinesterase (AChE) and acetylcholine (ACh) by enzyme-linked immunosorbent assay. Results:Compared with group C, the escape latency was significantly prolonged on the 3-5 training days, the frequency of crossing the platform and percentage of time of staying at the target quadrant were decreased, the content of AChE was increased, and the content of ACh was decreased in group K ( P<0.05). Compared with group K, the escape latency was significantly shortened on the 3-5 training days, the frequency of crossing the platform and percentage of time of staying at the target quadrant were increased, the content of AChE was decreased, and the content of ACh was increased in EK and G1K groups ( P<0.05). Compared with EK and G1K groups, the escape latency was significantly prolonged on the 3-5 training days, the frequency of crossing the platform and percentage of time of staying at the target quadrant were decreased, the content of AChE was increased, and the content of ACh was decreased in group G15EK ( P<0.05). Conclusion:GPR30 is involved in reduction of ketamine-induced long-term cognitive dysfunction by 17β estradiol, which is related to regulating the contents of AChE and ACh in hippocampi of neonatal rats.