PMID- 23534694 OWN - NLM STAT- MEDLINE DCOM- 20140120 LR - 20211021 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 19 IP - 7 DP - 2013 Jul TI - Rescue of cAMP response element-binding protein signaling reversed spatial memory retention impairments induced by subanesthetic dose of propofol. PG - 484-93 LID - 10.1111/cns.12088 [doi] AB - AIMS: The intravenous anesthetic propofol caused episodic memory impairments in human. We hypothesized propofol caused episodic-like spatial memory retention but not acquisition impairments in rats and rescuing cAMP response element-binding protein (CREB) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. METHODS: Male Sprague-Dawley rats were randomized into four groups: control; propofol (25 mg/kg, intraperitoneal); rolipram; and rolipram + propofol (pretreatment of rolipram 25 min before propofol, 0.3 mg/kg, intraperitoneal). Sedation and motor coordination were evaluated 5, 15, and 25 min after propofol injection. Invisible Morris water maze (MWM) acquisition and probe test (memory retention) were performed 5 min and 24 h after propofol injection. Visible MWM training was simultaneously performed to resist nonspatial effects. Hippocampal CREB signaling was detected 5 min, 50 min, and 24 h after propofol administration. RESULTS: Rolipram did not change propofol-induced anesthetic/sedative states or impair motor skills. No difference was found on the latency to the platform during the visible MWM. Propofol impaired spatial memory retention but not acquisition. Rolipram reversed propofol-induced spatial memory impairments and suppression on cAMP levels, CaMKIIalpha and CREB phosphorylation, brain-derived neurotropic factor (BDNF) and Arc protein expression. CONCLUSIONS: Propofol caused spatial memory retention impairments but not acquisition inability possibly by inhibiting CREB signaling. CI - (c) 2013 John Wiley & Sons Ltd. FAU - Zhang, Hao AU - Zhang H AD - Department of Anesthesiology and Neuroscience Research Center, Changzheng Hospital, Second Military Medical University, Shanghai, China. FAU - Zhang, Shao-Bo AU - Zhang SB FAU - Zhang, Qing-Qing AU - Zhang QQ FAU - Liu, Meng AU - Liu M FAU - He, Xing-Ying AU - He XY FAU - Zou, Zui AU - Zou Z FAU - Sun, Hai-Jing AU - Sun HJ FAU - You, Zhen-Dong AU - You ZD FAU - Shi, Xue-Yin AU - Shi XY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130328 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Anesthetics, Intravenous) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Hypnotics and Sedatives) RN - 0 (Phosphodiesterase Inhibitors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - K676NL63N7 (Rolipram) RN - YI7VU623SF (Propofol) SB - IM MH - *Anesthetics, Intravenous MH - Animals MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Cues MH - Cyclic AMP Response Element-Binding Protein/*physiology MH - Hypnotics and Sedatives MH - MAP Kinase Signaling System/drug effects MH - Male MH - Maze Learning/drug effects MH - Memory/drug effects/*physiology MH - Memory Disorders/*chemically induced/*physiopathology MH - Phosphodiesterase Inhibitors/pharmacology MH - Phosphorylation MH - Postural Balance/drug effects MH - *Propofol MH - Proto-Oncogene Proteins c-akt/metabolism MH - Radioimmunoassay MH - Rats MH - Rats, Sprague-Dawley MH - Rolipram/pharmacology MH - Signal Transduction/drug effects/*physiology MH - Space Perception/drug effects/*physiology PMC - PMC6493409 COIS- The authors declare no conflict of interests. EDAT- 2013/03/29 06:00 MHDA- 2014/01/21 06:00 PMCR- 2013/03/28 CRDT- 2013/03/29 06:00 PHST- 2012/11/25 00:00 [received] PHST- 2013/02/08 00:00 [revised] PHST- 2013/02/12 00:00 [accepted] PHST- 2013/03/29 06:00 [entrez] PHST- 2013/03/29 06:00 [pubmed] PHST- 2014/01/21 06:00 [medline] PHST- 2013/03/28 00:00 [pmc-release] AID - CNS12088 [pii] AID - 10.1111/cns.12088 [doi] PST - ppublish SO - CNS Neurosci Ther. 2013 Jul;19(7):484-93. doi: 10.1111/cns.12088. Epub 2013 Mar 28.