Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 24, Pages 6643-6650Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5126-05.2006
Keywords
leptin; glucocorticoids; endocannabinoids; neuroendocrine; stress; energy homeostasis
Categories
Funding
- NCRR NIH HHS [P20RR016816] Funding Source: Medline
- NIMH NIH HHS [MH066958] Funding Source: Medline
- NINDS NIH HHS [NS23002] Funding Source: Medline
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The hypothalamic paraventricular nucleus (PVN) integrates preautonomic and neuroendocrine control of energy homeostasis, fluid balance, and the stress response. We recently demonstrated that glucocorticoids act via a membrane receptor to rapidly cause endocannabinoid-mediated suppression of synaptic excitation in PVN neurosecretory neurons. Leptin, a major signal of nutritional state, suppresses CB1 cannabinoid receptor-dependent hyperphagia (increased appetite) in fasting animals by reducing hypothalamic levels of endocannabinoids. Here we show that glucocorticoids stimulate endocannabinoid biosynthesis and release via a G alpha(s)-cAMP protein kinase A-dependent mechanism and that leptin blocks glucocorticoid-induced endocannabinoid biosynthesis and suppression of excitation in the PVN via a phosphodiesterase-3B-mediated reduction in intracellular cAMP levels. We demonstrate this rapid hormonal interaction in both PVN magnocellular and parvocellular neurosecretory cells. Leptin blockade of the glucocorticoid-induced, endocannabinoid-mediated suppression of excitation was absent in leptin receptor-deficient obese Zucker rats. Our findings reveal a novel hormonal crosstalk that rapidly modulates synaptic excitation via endocannabinoid release in the hypothalamus and that provides a nutritional state-sensitive mechanism to integrate the neuroendocrine regulation of energy homeostasis, fluid balance, and the stress response.
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