Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala

• DOI: 10.1523/jneurosci.2279-15.2016
• Publication Date: 2016-08-10T16:12:57Z
• Authors: S. Di; C. A. Itoga; M. O. Fisher; J. Solomonow; E. A. Roltsch; N. W. Gilpin; J. G. Tasker
• Keywords: Basolateral amygdala; Retrograde signaling

Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids in basolateral amygdala (BLA). Cannabinoid receptors BLA contribute to anxiogenesis fear-memory formation. We tested for glucocorticoid-induced endocannabinoid regulation synaptic inhibition rat BLA. Glucocorticoid application slices elicited a rapid, nonreversible suppression spontaneous, but not evoked, GABAergic currents principal neurons; effect was also seen with membrane-impermeant glucocorticoid, intracellular glucocorticoid application, implicating membrane-associated receptor. The GABA blocked by antagonists nuclear corticosteroid receptors, or inhibitors gene transcription protein synthesis, inhibiting postsynaptic G-protein activity, suggesting nongenomic steroid signaling mechanism that stimulates release retrograde messenger. prevented blocking CB1 2-arachidonoylglycerol (2-AG) it mimicked occluded receptor agonists, indicating mediated 2-AG. neurons <i>in vitro</i> prior vivo</i> acute stress-induced, glucocorticoid-induced, endocannabinoid. Acute stress caused an increase anxiety-like behavior attenuated activation 2-AG synthesis Together, these findings suggest causes long-lasting via membrane receptor-induced at synapses, which contributes stress-induced anxiogenesis. <b>SIGNIFICANCE STATEMENT</b> provide cellular (BLA) rats. demonstrate induction is synapses. initiated neurons. show increases endocannabinoid-dependent centered modulation transmission contributes, therefore, anxiety, may play role anxiety disorders amygdala.