期刊论文详细信息
Behavioral and Brain Functions
Differential effects of diazepam and MPEP on habituation and neuro-behavioural processes in inbred mice
Amber R Salomons3  Nathaly Espitia Pinzon4  Hetty Boleij3  Susanne Kirchhoff3  Saskia S Arndt3  Rebecca E Nordquist2  Lothar Lindemann1  Georg Jaeschke1  Will Spooren1  Frauke Ohl3 
[1] F. Hoffmann-La Roche Ltd. Pharmaceuticals Division, Discovery Neuroscience, Basel, Switzerland
[2] Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 7, Utrecht, CL, 3584, The Netherlands
[3] Rudolf Magnus Institute of Neuroscience, Universiteitsweg 100, Utrecht, CG, 3584, The Netherlands
[4] Department of Animals in Science and Society, Division of Animal Welfare and Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584, Utrecht, CM, The Netherlands
关键词: mGluR5 antagonist;    Cortisosterone;    C-Fos;    Benzodiazepines;    Behavior;    Anxiety;   
Others  :  797508
DOI  :  10.1186/1744-9081-8-30
 received in 2011-11-07, accepted in 2012-06-11,  发布年份 2012
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【 摘 要 】

Background

Previous studies have demonstrated a profound lack of habituation in 129P3 mice compared to the habituating, but initially more anxious, BALB/c mice. The present study investigated whether this non-adaptive phenotype of 129P3 mice is primarily based on anxiety-related characteristics.

Methods

To test this hypothesis and extend our knowledge on the behavioural profile of 129P3 mice, the effects of the anxiolyticdiazepam (1, 3 and 5 mg/kg) and the putative anxiolytic metabotropic glutamate receptor 5 (mGlu5R) antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP, 3, 10 and 30 mg/kg) treatment on within-trial (intrasession) habituation, object recognition (diazepam: 1 mg/kg; MPEP 10 mg/kg) and on the central-nervous expression of the immediate early gene c-Fos (diazepam: 1 mg/kg; MPEP 10 mg/kg) were investigated.

Results

Behavioural findings validated the initially high, but habituating phenotype of BALB/c mice, while 129P3 mice were characterized by impaired intrasession habituation. Diazepam had an anxiolytic effect in BALB/c mice, while in higher doses caused behavioural inactivity in 129P3 mice. MPEP revealed almost no anxiolytic effects on behaviour in both strains, but reduced stress-induced corticosterone responses only in 129P3 mice. These results were complemented by reduced expression of c-Fos after MPEP treatment in brain areas related to emotional processes, and increased c-Fos expression in higher integrating brain areas such as the prelimbic cortex compared to vehicle-treated 129P3 mice.

Conclusions

These results suggest that the strain differences observed in (non)adaptive anxiety behaviour are at least in part mediated by differences in gamma-aminobutyric acid- A and mGluR5 mediated transmission.

【 授权许可】

   
2012 Salomons et al.; licensee BioMed Central Ltd.

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