Effects of FG7142 and immobilization stress on the gene expression in the neocortex of mice.
Several psychiatric disorders are often precipitated or exacerbated by exposure to stressors. FG7142 (N-methyl-beta-carboline-3-carboxamide), a partial inverse agonist of benzodiazepine receptors, mimics the physiological (an increased release in the adrenal steroid hormone) and neurochemical (an enhanced neurotransmission of monoamines) changes induced by stressful stimuli. We examined the effects of FG7142 and immobilization stress on the gene expression of the mouse neocortex in order to obtain a new insight into the molecular stress-responsive system. The effect of FG7142 (20 mg/kg, i.p.) on the gene expression of the brain area was examined using a DNA microarray method. The genes showing a significant change in expression were investigated in further experiments using the quantitative RT-PCR method. There was an increase in the mRNA of seven genes in the neocortex of mice 1h after treatment with FG7142. In addition, there was an increase in the mRNAs of five of the seven genes (Fos, Cyr61, Btg2, Adamts1, and Gem) in the neocortex of mice exposed to the stress for 1h. The up-regulation of these five genes by both FG7142 and immobilization stress indicates that these genes may be involved in the stress-responsive system. Dysfunctions of the system may be associated with the pathophysiology of psychiatric disorders.
Kurumaji
Akeo
A
Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyou-ku, Tokyo 113-8519, Japan. 0724.psyc@tmd.ac.jp
Ito
Takashi
T
Ishii
Sumikazu
S
Nishikawa
Toru
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D003345:Corticosterone / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D002243:Carbolines; D018756:GABA Antagonists; D018757:GABA Modulators; D005442:Flumazenil; C035874:FG 7142; D012313:RNA; D003345:Corticosterone