Recruitment of prefrontal cortical endocannabinoid signaling by glucocorticoids contributes to termination of the stress response. J Neurosci 2011 Jul 20;31(29):10506-15
Date
07/22/2011Pubmed ID
21775596Pubmed Central ID
PMC3179266DOI
10.1523/JNEUROSCI.0496-11.2011Scopus ID
2-s2.0-79960676744 (requires institutional sign-in at Scopus site) 326 CitationsAbstract
The mechanisms subserving the ability of glucocorticoid signaling within the medial prefrontal cortex (mPFC) to terminate stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis are not well understood. We report that antagonism of the cannabinoid CB(1) receptor locally within the mPFC prolonged corticosterone secretion following cessation of stress in rats. Mice lacking the CB(1) receptor exhibited a similar prolonged response to stress. Exposure of rats to stress produced an elevation in the endocannabinoid 2-arachidonoylglycerol within the mPFC that was reversed by pretreatment with the glucocorticoid receptor antagonist RU-486 (20 mg/kg). Electron microscopic and electrophysiological data demonstrated the presence of CB(1) receptors in inhibitory-type terminals impinging upon principal neurons within layer V of the prelimbic region of the mPFC. Bath application of corticosterone (100 nm) to prefrontal cortical slices suppressed GABA release onto principal neurons in layer V of the prelimbic region, when examined 1 h later, which was prevented by application of a CB(1) receptor antagonist. Collectively, these data demonstrate that the ability of stress-induced glucocorticoid signaling within mPFC to terminate HPA axis activity is mediated by a local recruitment of endocannabinoid signaling. Endocannabinoid activation of CB(1) receptors decreases GABA release within the mPFC, likely increasing the outflow of the principal neurons of the prelimbic region to contribute to termination of the stress response. These data support a model in which endocannabinoid signaling links glucocorticoid receptor engagement to activation of corticolimbic relays that inhibit corticosterone secretion.
Author List
Hill MN, McLaughlin RJ, Pan B, Fitzgerald ML, Roberts CJ, Lee TT, Karatsoreos IN, Mackie K, Viau V, Pickel VM, McEwen BS, Liu QS, Gorzalka BB, Hillard CJAuthors
Cecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinQing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Christopher J. Roberts PhD, MD Associate Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsArachidonic Acids
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Corticosterone
Disease Models, Animal
Electric Stimulation
Endocannabinoids
Freezing Reaction, Cataleptic
Glycerides
Hormone Antagonists
In Vitro Techniques
Long-Term Synaptic Depression
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Microscopy, Electron, Transmission
Mifepristone
Patch-Clamp Techniques
Piperidines
Prefrontal Cortex
Pyramidal Cells
Pyrazoles
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Signal Transduction
Stress, Psychological
gamma-Aminobutyric Acid
