Involvement Of CRFRl And Adrenoreceptors Of PVN,CeA And LC In Hypoxia-induced Rat Anxiety-like Behavior

Background and ObjectiveHPA axis, one of the body’s most important stress response systems, plays an important role in stress response to maintain homeostasis of the body. Stress can upregulate the expression of CRF and CRFR1, and the over expression of CRF and CRFR1is one of critical mechanisms underlying anxiety. Norepinephrine (NE) is one of the upstream regulating factors of CRF and CRFR1. The expression of NE and its receptors can be regulated by stress, and upregulation of of NE and its receptors can further regulate the expression of CRF and CRFR1. Hypoxia stress can induce the body to produce a series of physical changes. Our lab have already confirmed that the hypoxia stress during pregnancy can induce adult male offsprings behave anxiously, and it was highly related to the upregulation of CRFR1in PVN. The aim of this study is to explore whether hypoxia stress can induce anxiety-like behavior in adult rats, and what is function of CRF and CRFR1, and whether NE and its receptors are involved in anxiety-induced anxiety-like behavior.Methods Adult male SD rats were used in the research.We investigated the effect of5km5d continuous hypoxia on behavior and gene expression. Open field test, light and dark box test and elevated plus maze test were used to detect whether hypoxia can induce rat anxiety-like behavior. We examed the expression level of CRF, CRFR1, al, a2, β1, β2, TH and DBH in paraventricular nucleus (PVN)、 central nucleus of amygdale (CeA) and locus coeruleus (LC) by the real-time quantitative PCR.We blocked the genes expression by PVN microinjection of siRNA. Then the animals were treated with hypoxia of5km for5d. After the hypoxia treatment, all animals’behaviors were tested to identify the modulation effect of CRFR1,α1A and β2on animal behavior.Results1.5km5d hypoxia treatment didn’t change the sport ability of adult male rats in open field test.2.5km5d hypoxia induced anxiety like behaviour of rat in light and dark box. The latency of first time entry into the dark box significantly decreased and the duration of stayed in dark box (total5min test) significantly decreased, and there was no change in the number of transits in hypoxia group rats.3.5km5d hypoxia induced anxiety like behaviour of rat in elevated plus maze. The number of entries to closed arms or to open arms or to total arm entries were significantly decreased in hypoxia treatment group, the percentage of time into the open arms were significantly decreased in rats of hypoxia.4. Hypoxia t significantly increased CRF and CRFR1mRNA expression in PVN, and hypoxia significantly upregulated the al, β1and β2mRNA level in PVN.5. Hypoxia significantly increasesd CRFR1, al, β1and β2mRNA expression in CeA.6. Hypoxia significantly increasesd CRFR1, al, β1and β2mRNA expression in LC, and increased TH and DBH mRNA level, but did not change in CRF mRNA level.7. CRFR1and adrenergic receptor may be involved in hypoxia-induced anxiety-like behavior in adult rats.Conclusions5km5d hypoxia induced anxiety-like behavior, and upregulated the gene expression of CRF, CRFR1, TH, DBH and adrenergic receptors in PVN、CeA and LC. The increased CRFR1,αl,β1,β2mRNA expression may be involved in hypoxia-induced anxiety-like behavior in adult rats.