Acute restraint stress enhances hippocampal endocannabinoid function via glucocorticoid receptor activation

• Published in: Journal of psychopharmacology (Oxford) Vol. 26; no. 1; p. 56
• Main Authors: Wang, Meina, Hill, Matthew N, Zhang, Longhua, Gorzalka, Boris B, Hillard, Cecilia J, Alger, Bradley E
• Format: Journal Article
• Language: English
• Published: United States 01.01.2012
• Subjects: Animals; Arachidonic Acids - metabolism; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - metabolism; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Cannabinoid Receptor Modulators - metabolism; Corticosterone - pharmacology; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Endocannabinoids; gamma-Aminobutyric Acid - metabolism; Glycerides - metabolism; Inhibitory Postsynaptic Potentials - drug effects; Inhibitory Postsynaptic Potentials - physiology; Male; Nifedipine - pharmacology; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid - metabolism; Receptors, Muscarinic - metabolism; Stress, Psychological - metabolism
• ISSN: 1461-7285
• DOI: 10.1177/0269881111409606

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.