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To identify genes involved in the development of anxiety or fear, we analyzed the gene expression profiles of the cortex of anxious hooded PVG and Sprague-Dawley (SD) rats after exposure to the cat-freezing test apparatus. These two rat strains showed a marked difference in the extent of anxious behavior on the cat-freezing test; the hooded PVG rats showed highly anxious behavior while a low anxiety state was observed in SD rats. A cDNA microarray consisting of 5,931 genes was employed to investigate the global mRNA expression profiles of anxiety-related genes. According to the assumption that an abundance ratio of > or =1.5 is indicative of a change in gene expression, we detected 16 upregulated and 38 downregulated genes in PVG hooded and SD rats. Some of these genes have not yet been associated with anxiety (e.g. FGF), while other genes were recently found to be expressed in an anxious state (e.g., rat nerve growth factor-induced gene, NGFI-A). Our study also focused on the expression of some neurotransmitter receptors that have already been proven to be relevant to anxiety or fear, e.g., gamma-aminobutyric acid (GABA), cholecystokinin (CCK) and 5-HT(3) receptors. To further confirm the microarray data, the mRNA expressions of three genes: rat activity-regulated cytoskeleton-associated gene (Arc), rat NGFI-A gene and rat 5-HT(3) receptor (5-HT(3)R) mRNA, were studied by reverse transcription-polymerase chain reaction (RT-PCR). The results of RT-PCR were basically consistent with those from cDNA microarray. Our study therefore demonstrated that the microarray technique is an efficient tool for analyzing global expression profiles of anxiety-related genes, which may also provide further insight into the molecular mechanisms underlying the states of anxiety and fear.

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