Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164, USA.
Life Sci. 2012 Feb 13;90(7-8):267-71. doi: 10.1016/j.lfs.2011.11.010. Epub 2011 Dec 1.
We studied whether hyperbaric oxygen (HBO(2)) treatment, which is known to increase production of nitric oxide (NO) in the brain, might also produce an NO-dependent anxiolytic-like behavioral response.
Male NIH Swiss mice (20-25g) were subjected to a 60-min HBO(2) treatment at different absolute atmospheres, and anxiety was assessed using the light/dark exploration test at different time intervals following the cessation of HBO(2) treatment. To ascertain the underlying mechanism of action, other groups of mice were pretreated with the NO synthase inhibitor N(G)-monomethyl-l-arginine acetate, the NO scavenger 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (carboxy-PTIO), the soluble guanylyl cyclase-inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or the benzodiazepine antagonist flumazenil to determine their influence on the HBO(2)-induced anxiolytic-like effect.
A 60-min HBO(2) treatment at 3.0 absolute atmospheres increased the time spent by mice in the light compartment that lasted up to 90 min following the end of HBO(2) treatment. This anxiolytic effect of HBO(2) was significantly reduced by pretreatment with L-NMMA, carboxy-PTIO, ODQ and flumazenil.
Based on these findings, we conclude that a 60-min HBO(2) treatment is capable of inducing an anxiolytic effect that possibly involves NO, cyclic GMP and the benzodiazepine binding site.
我们研究了高压氧(HBO(2))治疗是否会增加大脑中一氧化氮(NO)的产生,以及是否会产生依赖于 NO 的抗焦虑样行为反应。
雄性 NIH 瑞士小鼠(20-25g)接受不同绝对大气压的 60 分钟 HBO(2)治疗,在 HBO(2)治疗停止后不同时间间隔使用明暗探索试验评估焦虑。为了确定作用的潜在机制,其他组的小鼠用一氧化氮合酶抑制剂 N(G)-单甲基-L-精氨酸乙酸盐、一氧化氮清除剂 2-(4-羧基苯基)-4,5-二氢-4,4,5,5-四甲基-1H-咪唑基-1-氧基-3-氧化物(羧基-PTIO)、可溶性鸟苷酸环化酶抑制剂 1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮(ODQ)或苯二氮䓬拮抗剂氟马西尼预处理,以确定它们对 HBO(2)诱导的抗焦虑样效应的影响。
3.0 绝对大气压下 60 分钟 HBO(2)治疗可增加小鼠在光照室中的停留时间,这种抗焦虑作用可持续到 HBO(2)治疗结束后 90 分钟。L-NMMA、羧基-PTIO、ODQ 和氟马西尼预处理显著降低了 HBO(2)的这种抗焦虑作用。
基于这些发现,我们得出结论,60 分钟 HBO(2)治疗能够诱导抗焦虑作用,该作用可能涉及一氧化氮、环鸟苷酸和苯二氮䓬结合位点。