TITLE:
Ro 20-1724 Ameliorates Learning Deficit and Long-Term Memory Impairment Secondary to Repeated Ketamine Anesthesia in Young Rats
AUTHORS:
Sheng Peng, Hai Yan Sun, Gong-Jian Liu, Xia Yang, George Mychaskiw II
KEYWORDS:
Research; Animal; Anesthesia; Neurodegeneration; Phsophodisterase Inhibitors; Memory
JOURNAL NAME:
Neuroscience and Medicine,
Vol.4 No.3,
September
11,
2013
ABSTRACT: To investigate effects and possible
mechanism of Ro 20-1724, a PDE4 inhibitor, on long-time learning and memory
ability following repeated ketamine exposure in immature rats. Methods: Sixty 21-day-old SD rats were randomly divided into five groups (n = 12): C: Normal control group, S:
Saline control group, K: Ketamine, K + Ro:Ketamine + Ro 20-1724, K + E: Ketamine + ethanol vehicle. Ro 20-1724
(0.5 mg·kg-1) or its vehicle (ethanol) was administered intraperitoneally 30 minutes after
ketamine anesthesia (70 mg·kg-1), daily for seven days. Nine weeks after
birth, the Morris water maze was used to test the ability of
learning and spatial localization memory on the rats. Following behavioral testing, animals’ hippocampi
were removed for Western blot and electron microscopic examination. Results: In the Morris water maze test, compared with
controls, the escape latency in groups exposed to ketamine or ketamine plus the
ethanol vehicle were significantly prolonged (P P P 0.05), while there was no significant
difference between
control groups and animals treated with Ro 20-1724 following ketamine exposure
(P > 0.05). Electron microscopy
demonstrated degenerative changes in hippocampal neurons of animals
repetitively exposed to 70 mg·kg-1 Ketamine, which was ameliorated by Ro 20-1724 (0.5 mg·kg-1). Conclusion: The PDE-4 inhibitor Ro 20-1724 (0.5 mg·kg-1