Analysis of the Stress Response in Rats Trained in the Water-Maze: Differential Expression of Corticotropin-Releasing Hormone, CRH-R1, Glucocorticoid Receptors and Brain-Derived Neurotrophic Factor in Limbic RegionsAguilar-Valles A. · Sánchez E. · de Gortari P. · Balderas I. · Ramírez-Amaya V. · Bermúdez-Rattoni F. · Joseph-Bravo P.
aDepartamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), bDivisión de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñíz, México, cDepartamento de Neurociencias, Instituto de Fisiología Celular, UNAM, and dDepartamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, UNAM, Mexico
Glucocorticoids and corticotropin-releasing hormone (CRH) are key regulators of stress responses. Different types of stress activate the CRH system; in hypothalamus, CRH expression and release are increased by physical or psychological stressors while in amygdala, preferentially by psychological stress. Learning and memory processes are modulated by glucocorticoids and stress at different levels. To characterize the kind of stress provoked by a hippocampal-dependent task such as spatial learning, we compared the expression profile of glucocorticoid receptor (GR), pro-CRH and CRH-R1 mRNAs (analyzed by RT-PCR), in amygdala, hippocampus and hypothalamus and quantified serum corticosterone levels by radioimmunoassay at different stages of training. mRNA levels of brain-derived neurotrophic factor (BDNF) were also quantified due to its prominent role in learning and memory processes. Male Wistar rats trained for 1, 3 or 5 days in the Morris water-maze (10 trials/day) were sacrificed 5–60 min the after last trial. A strong stress response occurred at day one in both yoked and trained animals (increased corticosterone and hypothalamic pro-CRH and CRH-R1 mRNA levels); changes gradually diminished as the test progressed. In amygdala, pro-CRH mRNA levels decreased while those of BDNF augmented when stress was highest, in yoked and trained animals. Hippocampi, of both yoked and trained groups, had decreased levels of GR mRNA on days 1 and 3, normalizing by day 5, while those of pro-CRH and CRH-R1 increased after the 3rd day. Increased gene expression, specifically due to spatial learning, occurred only for hippocampal BDNF since day 3. These results show that the Morris water-maze paradigm induces a strong stress response that is gradually attenuated. Inhibition of CRH expression in amygdala suggests that the stress inflicted is of physical but not of psychological nature and could lead to reduced fear or anxiety.
Instituto de Biotecnología, UNAM, AP510-3
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Received: December 13, 2005
Accepted after revision: March 14, 2006
Published online: May 4, 2006
Number of Print Pages : 14
Number of Figures : 5, Number of Tables : 0, Number of References : 61
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Vol. 82, No. 5-6, Year 2005 (Cover Date: May 2006)
Journal Editor: Kordon, C. (Paris)
ISSN: 0028–3835 (print), 1423–0194 (Online)
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