title: Desipramine prevents the sustained increase in corticotropin-releasing hormone-like immunoreactivity induced by repeated immobilization stress in the rat central extended amygdala.
abstract: Clinical and experimental studies have shown that the activation of corticotropin-releasing hormone (CRH) and noradrenergic systems mediate stress-induced anxiety. Repeated immobilization stress (RIS) has been shown to induce long-lasting anxiety behavior and changes in noradrenaline turnover. The present work was aimed at studying the effect of RIS on the in situ expression of CRH-LI in the central extended amygdala and paraventricular nucleus of the hypothalamus (PVN). Our results showed that RIS for 15 days induces a significant increase of CRH-LI expression in the central extended amygdala. The increase in CRH-LI expression in the central extended amygdala was sustained even after a 25-day stress-free period. The concomitant administration of desipramine (DMI), a specific noradrenaline uptake inhibitor, fully prevented the RIS-induced increase in CRH expression. RIS also induced an increase of CRH-LI expression in the PVN that was prevented by the concomitant DMI administration. In contrast to the sustained effect observed in the central extended amygdala, the RIS-induced increase of CRH-LI expression in the PVN was nonlasting. DMI administration also prevented the RIS-induced increase of adrenal gland weight. The present findings showing that RIS induces a sustained increase of CRH expression in the central extended amygdala suggest that the repeated activation of CRH neurons and CRH receptors in the central extended amygdala may underlie the long-lasting anxiety behavior induced by RIS. Further studies should address the mechanisms involved in the effect of DMI and its eventual relevance in the therapeutic actions of DMI.
authors.affiliation: Department of Cell and Molecular Biology, Faculty of Biological Sciences, Catholic University of Chile, Santiago, Chile.
authors.forename: Marcos
authors.initials: M
authors.lastname: Santibañez
authors.forename: Katia
authors.initials: K
authors.lastname: Gysling
authors.forename: María Inés
authors.initials: MI
authors.lastname: Forray
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001007:Anxiety / Q000523:psychology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000378:metabolism*; D003891:Desipramine / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D000929:Antidepressive Agents, Tricyclic; D003346:Corticotropin-Releasing Hormone; D003891:Desipramine