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EndocannabinoidSignaling NegativelyModulatesStress-InducedActivation of theHypothalamic-Pituitary-Adrenal Axis Sachin PatelCraig T. RoelkeDavid J. Rademacher2004 год

Endocannabinoid Signaling Negatively Modulates Stress-Induced Activation of the Hypothalamic-Pituitary-Adrenal Axis
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Страница публикацииПубликация в OpenAlex
Аннотация: Activation of the hypothalamic-pituitary-adrenal (HPA) axis is critical for the adaptation and survival of animals upon exposure to stressful stimuli, and data suggest that endocannabinoid (eCB) signaling modulates neuroendocrine function. We have explored the role of eCB signaling in the modulation of stress-induced HPA axis activation. Administration of the CB1 receptor antagonist/inverse agonist SR141716 (0.01, 0.1, 1, and 5 mg/kg, i.p.) to male mice produced a small, dose-dependent increase in the serum corticosterone (CORT) concentration. Despite this effect, the highest dose of SR141716 did not significantly increase neuronal activity within the paraventricular nucleus of the hypothalamus, as measured by the induction of Fos protein. Similarly, exposure of mice to 30 min of restraint increased serum CORT concentrations, but did not produce a consistent, statistically significant increase in Fos expression within the PVN. However, pretreatment of mice with SR141716 before restraint stress robustly potentiated restraint-induced CORT release and Fos expression within the PVN. Pretreatment of mice with either the CB1 receptor agonist CP55940, the eCB transport inhibitor AM404, or the fatty acid amide hydrolase inhibitor URB597 significantly decreased or eliminated restraint-induced CORT release. Upon exposure to acute restraint, hypothalamic 2-arachidonylglycerol content was reduced compared with the control value; however, after 5 d of restraint exposure (which resulted in an attenuated CORT response), the hypothalamic 2-arachidonylglycerol content was increased compared with the control value. These data indicate that eCB signaling negatively modulates HPA axis function in a context-dependent manner and suggest that pharmacological augmentation of eCB signaling could serve as a novel approach to the treatment of anxiety-related disorders.
Год издания: 2004
Авторы: Sachin Patel, Craig T. Roelke, David J. Rademacher, William E. Cullinan, Cecilia J. Hillard
Издательство: Oxford University Press
Источник: Endocrinology
Ключевые слова: Cannabis and Cannabinoid Research, Dietary Effects on Health, Regulation of Appetite and Obesity
Другие ссылки: Endocrinology (HTML)
PubMed (HTML)