Inhibitory effect of propofol on ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation
Background: Non‐competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonists, including ketamine, have psychotomimetic activities and cause neuronal damage in the posterior cingulate and retrosplenial cortices (PC/RS), which are suggested to be the brain regions responsible for their psychotomimeti...
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Published in | Acta anaesthesiologica Scandinavica Vol. 47; no. 3; pp. 284 - 290 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Munksgaard International Publishers
01.03.2003
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | Background: Non‐competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonists, including ketamine, have psychotomimetic activities and cause neuronal damage in the posterior cingulate and retrosplenial cortices (PC/RS), which are suggested to be the brain regions responsible for their psychotomimetic activities. We previously demonstrated that ketamine induced marked c‐Fos (c‐fos protein) expression in the rat PC/RS, which was inhibited by propofol, and the expression was closely related to ketamine‐induced abnormal behavior. In the present study, we investigated whether the inhibition by propofol was mediated by GABAA receptor receptor activation.
Methods: Using Wistar rats, propofol alone, propofol with bicuculline or propofol with flumazenil was injected intravenously and then continuously infused. Fifteen minutes later, 100 mg kg−1 of ketamine or normal saline was injected intraperitoneally. Two hours after the ketamine or saline injection, the brain was extracted and brain sections were prepared, and c‐Fos expression was detected using immunohistochemical methods.
Results: Ketamine induced marked c‐Fos expression in the PC/RS (171 ± 9/0.4 mm2), which was significantly inhibited by propofol (5 ± 5/0.4 mm2). The inhibition by propofol was disinhibited dose‐dependently by both bicuculline (0.5 and 1.0 mg kg−1 bicuculline groups: 46 ± 15 and 143 ± 16, respectively) and flumazenil (0.1 and 1.0 mg kg−1 flumazenil groups: 79 ± 6 and 130 ± 15, respectively).
Conclusion: These results demonstrate that the inhibitory effect of propofol on ketamine‐induced c‐Fos expression in the PC/RS is mediated by GABAA receptor activation, and suggests that ketamine‐induced psychoneuronal adverse effects may be suppressed by propofol via the activation of GABAA receptors. |
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Bibliography: | ArticleID:AAS040 ark:/67375/WNG-3PG3G3DR-H istex:743C947B0DFDD7CE856191F33DE003AAF108F3A9 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0001-5172 1399-6576 |
DOI: | 10.1034/j.1399-6576.2003.00040.x |