Sirvi Kuupäev , alustades "2010-05-07T11:52:47Z" järgi

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Role of endocannabinoid system and Wfs1 in regulation of emotional behaviour: behavioural, pharmacological and genetic studies
(2010-05-07T11:52:47Z) Sütt, Silva
Anxiety disorders are the most prevalent psychiatric disorders. The molecular mechanisms of the development of anxiety disorders are largely unknown, therefore possible new therapeutic targets in the brain were investigated. In the present study we used cat odour and the elevated plus-maze exposure to elicit anxiety-like response in Wistar rats or Wfs1 gene-deficient mice. For gene expression analysis of the endocannabinoid system (ECS), Wfs1, Gabra1 and Gabra2 genes quantitative real-time-PCR was performed. We found that only strong stress – cat odour exposure – increased some ECS genes in the mesolimbic area, but decreased their expression in the amygdala and in periaqueductal gray matter. This is probably related with different activation of brain structures in response to anxiety. High exploratory activity rats had reduced expression of Wfs1 mRNA in the mesolimbic area and hippocampus, whereas low exploratory activity rats displayed inhibited expression of the Wfs1 gene in the temporal lobe compared to control group animals. Increased anxiety after cat odour exposure in C57Bl/6 mice was accompanied by decreased level of the Wfs1 gene in the mesolimbic area and temporal lobe. Female Wfs1-deficient mice displayed increased anxiety and sensitivity to the anxiolytic action of diazepam and ethanol. This is related to the reduced level of Gabra1 and Gabra2 mRNA expression in the frontal cortex and in temporal lobe. In the present study we found that ECS and Wfs1 protein are playing a major role in the adaptation of rodents to a novel and aversive environment.