Long-term regulation of locus ceruleus sensitivity to corticotropin-releasing factor by swim stress

作     者：Curtis, AL Pavcovich, LA Valentino, RJ 

作者机构：Med Coll Penn & Hahnemann Univ Dept Psychiat Philadelphia PA 19102 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第289卷第3期

页      面：1211-1219页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NIMH NIH HHS [MH40008  MH42796  MH00840] Funding Source: Medline 

主　　题：动作电位/药物作用 动作电位/生理学 方差分析 促肾上腺皮质素释放激素/投药和剂量 促肾上腺皮质素释放激素/药理学 输注 胃肠外 蓝斑/药物作用 蓝斑/生理学 蓝斑/病理生理学 神经元/药物作用 神经元/生理学 大鼠 Sprague-Dawley 绵羊 应激 心理学 游泳 时间因素 血管活性肠肽/药理学 动物 男(雄)性 大鼠 

摘      要：Corticotropin-releasing factor (CRF) acts as a putative neurotransmitter in the locus ceruleus (LC) to mediate its activation by certain stressors. In this study, we quantified LC sensitivity to CRF 24 h after swim stress, at a time when behavioral depression that is sensitive to antidepressants is apparent. Rats were placed in a tank with 30 cm (swim stress) or 4 cm water and 24 h later, either behavior was monitored in a forced swim test or LC discharge was recorded. Swim stress rats were more immobile than control animals in the swim test. LC neurons of swim stress rats were sensitized to low doses of CRF (0.1-0.3 mu g i.c.v.) that were ineffective in control animals and were desensitized to higher doses. Swim stress selectively altered LC sensitivity to CRF because neither LC spontaneous discharge nor responses to other agents (e.g., carbachol, vasoactive intestinal peptide) were altered. Finally, the mechanism for sensitization was localized to the LC because neuronal activation by low doses of CRF was prevented by the intracerulear administration of a CRF antagonist. CRF dose-response curves were consistent with a two-site model with similar dissociation constants under control conditions but divergent dissociation constants after swim stress. The results suggest that swim stress (and pert-caps other stressors) functionally alters CRF receptors that have an impact on LC activity. Stress-induced regulation of LC sensitivity to CRF may underlie behavioral aspects of stress-related psychiatric disorders.