The endocannabinoid system in guarding against fear, anxiety and stress

Abstract

The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment. eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders. An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.

Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation

“…Thus, glucocorticoids enhance the production of endocannabinoids to counteract the activity of the HPA axis in many brain regions, including the hippocampus, the prefrontal cortex, and the hypothalamus (16,24). Overall, endocannabinoid production is induced by acute stress and acts by buffering stress-induced behavioral and endocrine stress effects (16,17,23).In this study we reveal a mechanism mediating stress-induced impairment of object-recognition memory consolidation. Using a combination of acute systemic and local pharmacological approaches and newly generated mouse lines, we found that peripheral and hippocampal CB1 receptors in dopamine β-hydroxylase (DBH)-expressing cells (i.e., adrenergic/noradrenergic cells) are both necessary and sufficient to impair object-recognition memory consolidation produced by acute stress.…”

“…Moreover, the endocannabinoid system also participates in the negative feedback regulation of the HPA axis after stress (13, 23). Thus, glucocorticoids enhance the production of endocannabinoids to counteract the activity of the HPA axis in many brain regions, including the hippocampus, the prefrontal cortex, and the hypothalamus (16,24). Overall, endocannabinoid production is induced by acute stress and acts by buffering stress-induced behavioral and endocrine stress effects (16,17,23).…”

“…The endocannabinoid system is an endogenous neuromodulatory system playing a relevant role in the regulation of the stress response (13)(14)(15)(16)(17)(18). Endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and N-arachidonoyl ethanolamine (anandamide; AEA), act mainly at two types of cannabinoid receptors, cannabinoid type-1 (CB1) and type-2 (CB2) receptors.…”

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

“…The neurobiological actions of endogenous cannabinoidlike compounds have been described from molecular to behavioral approaches (Pertwee, 2006(Pertwee, , 2015Scherma et al, 2014;Katona, 2015;Lutz et al, 2015;Manduca et al, 2015;Velasco et al, 2015;Lu and Mackie, 2016;Nikan et al, 2016;Wang et al, 2016). Since anandamide was the very first endocannabinoid described (Devane et al, 1992), it has been the focus of attention due to that it resembles the pharmacological effects of principal compound of Cannabis sativa, D 9 -THC, by behaving as a natural ligand for the CB 1 cannabinoid receptor (Console-Bram et al, 2012).…”

Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents

“…8,15 Various lines of evidence led to the hypothesis that stress increases FAAH activity to reduce AEA concentrations, which increases the excitability of BLA principal neurons due to the unavailability of AEA for its suppression of glutamate release, leading to anxiety development. 16,22,23 Therefore, FAAH inhibitors could produce anti-anxiety effects through decreased excitability of BLA principal neurons following AEA suppression of glutamate release. 16,22,23 However, here we found results suggesting that FAAH inhibitors produce anti-anxiety effects through long-term depression (LTD) after sequential activation of astroglial CB 1 R and postsynaptic glutamate receptors at PFC-BLA synapses.…”