ABSTRACT
Objective To observe a new phosphodiesterase-4 inhibitor Ro 20-1724 on ketamine anesthesia-induced learning and memory impairment and cAMP/PKA-CREB-BDNF signal pathway in immature rats.Methods Twenty-four 21 day-old SD rats were randomly divided into 4 groups (n=6 each):control group (group C) ;ketamine group (group K) ;ketamine+Ro 20-1724 group(group K+Ro) and ketamine+vehicle (0.1％ ethanol) group (group K+E).Ketamine 70 mg/kg was injected intraperitoneally(IP) once a day for 7 consecutive days in groups K,K+Ro,and K+E.Ro 20-1724 0.5 mg/kg and equal volume of vehicle were injected IP at 30 min after IP ketamine each time respectively.Morris water maze was used to assess learning and memory ability after 2 days normal feeding,the escape latency and frequency of passing the platform were recorded.The animals were killed after water maze test and the cAMP,PKA,p-CREB,and BDNF protein expression in hippocampus were detected.Results Repetitive ketamine anesthesia significantly prolonged the escape latency (P＜0.01),decreased the frequency of passing the platform(P＜0.01),and down-regulated the expression of cAMP,PKA,p-CREB,and BDNF protein ((280±31) pmol/mg vs (210± 19) mol/mg,P＜0.01 ; 1.32±0.11 vs 1.13±0.12,P＜0.01 ; 2.61 ±0.22 vs 2.03 ± ±0.19,P＜0.01 ; 1.51 ±0.14 vs 1.16±0.10,P＜0.05) ; Compared with group K,Ro 20-172,significantly attenuated the escape latency time(P＜0.05,P＜0.01)and increased the frequency of passing the platform(P＜0.01),and ameliorated the expression of cAMP,PKA,p-CREB,and BDNF protein ((210± 19) pmoL/mg vs (240± 27) pmol/mg,P ＜0.05;1.13±0.12 vs 1.28±0.12,P＜0.05;2.03±0.19 vs 2.32±0.21,2.32±0.21;1.16±0.10 vs 1.37±0.11,P＜0.01).There was no difference between group K+Ro and group C,and between group K+E and group K(P＞0.05).Conclusion ketamine anesthesia-induced learning and memory impairment can be improved by Ro 20-1724,and cAMP/PKA-CREB-BDNF signal pathway in hippocampus participated in the changes.
ABSTRACT
Objective To observe the effect of Ro 20-1724 on social interaction ability of developing rats after repeated ketamine anesthesia.Methods 32 rats with 21 days old were randomly divided into four groups,control group (C group),ketamine group (K group),ketamine + Ro 20-1724 group (K + R group),ketamine + ethanol group (K + E group).Ethanol was used as a solvent of Ro 20-1724.Ketamine 70 mg· kg-1 was intraperitoneal injected,30 min later,to give or not give Ro 20-1724 0.5 mg · kg-1 or equivalent ethanol solvent for once each day for seven consecutive days.Then the rats were fed for three days.On the fourth day after the last administration,the social interaction ability were assessed in all rats.The expression of brain-derived neurotropic factor (BDNF) in hippocampal CA1 region was detected using conventional ELISA.Results Comparing with rats in C group,the time spent on the cage of lifeless body ((60 ± 29) min vs (109 ± 33) min,P ＜ 0.01),unfamiliar rats (103 ±35)min vs (151 ±42)min,P＜0.01;((123 ±34)min vs (184 ±46) min,P＜0.05) and familiar rats (89 ± 25) min vs (140 ± 38) min,P ＜ 0.01) in the social interaction test was significantly less in K group.The time spent significantly prolonged in group K + R,comparing with K group (lifeless body:(94 ± 34) min vs (60 ±29) min,P＜0.01) ;unfamiliar rat 1:(140 ±41) min vs (103 ±35)min,P＜0.05) ;unfamiliar rat 2:(171 ±45)min vs (123 ±34)min,P＜0.01) ; familiar rat:(133 ±35)min vs (89 ±25) min,P＜0.01).And there was no difference between K group and K + N group (P ＞ 0.05).The expression of BDNF in hippocampal CA1 region was significantly lower in K group,comparing with C group ((8.6 ± 2.7) ng/ml vs (11.8 ± 2.4) ng/ml,P ＜0.01) ; and there was a significant increase in K + R group,comparing with K group ((10.1 ± 3.6) ng/ml vs (8.6 ± 2.7) ng/ml,P ＜ 0.05).Conclusion Ro 20-1724 significant rescued social interaction impairment induced by ketamine anesthesia in developing rats.And BDNF in hippocampal CA1 region contribute to the reversal process.