Open AccessRescue of c AMP Response Element‐Binding Protein Signaling Reversed Spatial Memory Retention Impairments Induced by Subanesthetic Dose of Propofol
Author(s) -
Zhang Hao,
Zhang ShaoBo,
Zhang QingQing,
Liu Meng,
He XingYing,
Zou Zui,
Sun HaiJing,
You ZhenDong,
Shi XueYin
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12088
Subject(s) - rolipram , creb , propofol , morris water navigation task , pharmacology , cyclic amp response element binding protein , hippocampus , intraperitoneal injection , phosphodiesterase , neuroscience , anesthesia , medicine , chemistry , endocrinology , psychology , biochemistry , transcription factor , gene , enzyme
Summary 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 c AMP response element‐binding protein ( CREB ) signaling using selective type IV phosphodiesterase (PDEIV) inhibitor rolipram reversed these effects. Methods Male S prague‐ D awley 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. R olipram reversed propofol‐induced spatial memory impairments and suppression on c AMP levels, C a MKII α 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.