Faculty Collaboration Database

Acute restraint stress enhances hippocampal endocannabinoid function via glucocorticoid receptor activation. J Psychopharmacol 2012 Jan;26(1):56-70

Date

09/06/2011

Pubmed ID

21890595

Pubmed Central ID

PMC3373303

DOI

10.1177/0269881111409606

Scopus ID

2-s2.0-84863011182 (requires institutional sign-in at Scopus site)   112 Citations

Abstract

Exposure to behavioural stress normally triggers a complex, multilevel response of the hypothalamic-pituitary-adrenal (HPA) axis that helps maintain homeostatic balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic stress, few studies have directly addressed its response to acute stress. Here we show that acute restraint stress enhances eCB-dependent modulation of GABA release measured by whole-cell voltage clamp of inhibitory postsynaptic currents (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro. Both Ca(2+)-dependent, eCB-mediated depolarization-induced suppression of inhibition (DSI), and muscarinic cholinergic receptor (mAChR)-mediated eCB mobilization are enhanced following acute stress exposure. DSI enhancement is dependent on the activation of glucocorticoid receptors (GRs) and is mimicked by both in vivo and in vitro corticosterone treatment. This effect does not appear to involve cyclooxygenase-2 (COX-2), an enzyme that can degrade eCBs; however, treatment of hippocampal slices with the L-type calcium (Ca(2+)) channel inhibitor, nifedipine, reverses while an agonist of these channels mimics the effect of in vivo stress. Finally, we find that acute stress produces a delayed (by 30 min) increase in the hippocampal content of 2-arachidonoylglycerol, the eCB responsible for DSI. These results support the hypothesis that the ECS is a biochemical effector of glucocorticoids in the brain, linking stress with changes in synaptic strength.

Author List

Wang M, Hill MN, Zhang L, Gorzalka BB, Hillard CJ, Alger BE

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Arachidonic Acids
CA1 Region, Hippocampal
Calcium
Calcium Channel Blockers
Calcium Channels
Cannabinoid Receptor Modulators
Corticosterone
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Endocannabinoids
Glycerides
Inhibitory Postsynaptic Potentials
Male
Nifedipine
Pyramidal Cells
Rats
Rats, Sprague-Dawley
Receptors, Glucocorticoid
Receptors, Muscarinic
Stress, Psychological
gamma-Aminobutyric Acid