The anxiolytics CI-988 and chlordiazepoxide fail to reduce immediate early gene mRNA stimulation following exposure to the rat elevated X-maze.
This study uses immediate early transcription factor gene expression to map neuronal activation after a single exposure to the elevated X-maze. Exposure to this novel environment leads to widespread upregulation in the gene expression of c-fos, NGFI-A and NGFI-B (the nerve growth factor induced genes), but not c-jun nor jun B as shown by in situ hybridization and northern blot analysis. Changes in c-fos were evident after just 5 min exposure to the maze. The cholecystokininB receptor antagonist, CI-988, given intraperitoneally at 1 mg/kg 40 min prior to exposure to the X-maze demonstrated an anxiolytic profile without affecting overall movement around the maze, however it did not reduce the increased levels of gene expression with the methodology used. Likewise the anxiolytic benzodiazepine, chlordiazepoxide at 3 mg/kg did not reduce gene expression. It is concluded that a reduction in an index of behavioural stress/anxiety produced by anxiolytic agents is not concomitantly followed by a detectable reduction in immediate early gene induction.
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, UK.
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GL
Hinks
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Brown
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Field
J A
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Poat
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Hughes
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D015533:Transcriptional Activation
D014151:Anti-Anxiety Agents; D007211:Indoles; D012333:RNA, Messenger; C065599:PD 134308; D008536:Meglumine; D002707:Chlordiazepoxide