The effects anandamide signaling in the prelimbic cortex and basolateral amygdala on coping with environmental stimuli in rats

Abstract

RATIONALE: Several lines of recent evidence suggest that endocannabinoids affect behavior by influencing the general patterns of challenge responding. OBJECTIVES: Here we investigated the brain mechanisms underlying this phenomenon in rats. METHODS: The anandamide hydrolysis inhibitor URB597 was condensed into the tip of stainless steel cannulae, which were chronically implanted slightly above the prelimbic cortex (PRL) or the basolateral amygdala (BLA), two important regions of coping and endocannabinoid action. Thereafter we investigated behavioral responsiveness to ambient light level in the elevated plus-maze and conditioned fear tests. RESULTS: URB597 concentration was ~30 μg/mg protein in target areas; local brain anandamide levels increased threefold, without significant changes in 2-arachidonoylglycerol.High levels of illumination halved the time spent by controls in the open arms of the plus-maze.No similar decrease was observed in rats with URB597 implants in the PRL. High light decreased conditioned fear by 30% in controls, but not in rats with prelimbic URB597 implants.Unresponsiveness to environmental challenges was not attributable to the anxiolytic effects of anandamide enhancement, as implants induced paradoxical anxiogenic-like effects under low light, which could be explained by effects on stimulus responsiveness rather than by effects on anxiety.URB597 implants targeting the BLA did not affect stimulus responsiveness. CONCLUSIONS:Our findings show that elevated prelimbic anandamide signaling leads to less environmentdependent (more autonomous) behavioral responses to challenges, which is an attribute of active coping styles. These findings are discussed in light of two emerging concepts of endocannabinoid roles, particularly "emotional homeostasis" and "active coping".

Association of the Fatty Acid Amide Hydrolase C385A Polymorphism With Alcohol Use Severity and Coping Motives in Heavy‐Drinking Youth

“…However, the anxiolytic effects of decreased FAAH activity are notably more prominent under conditions of high environmental aversiveness (Patel et al, 2017) and FAAH inhibition has also been shown to attenuate stress‐induced reductions in salience and reward‐seeking behavior (Rademacher et al, 2008). Further, FAAH and endocannabinoid tone may influence coping behavior such that FAAH inhibition and increased anandamide promote more focused problem solving in light of anxiety‐inducing environmental stimuli (Aliczki et al, 2016). Finally, alcohol‐related stress response has been shown to be context‐dependent, whereby acute alcohol intoxication dampens aversive stress reactivity to uncertain or variable threat (Bradford et al, 2013; Gorka et al, 2020).…”

Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening

“…In addition to being directly involved in modulating the neuroendocrine stress response, prefrontocortical eCB signaling has been highly implicated in regulating the emotional and behavioral responses to stress exposure. For example, inhibiting AEA hydrolysis in the PL (thereby boosting levels) is able to significantly reduce stress-induced corticosterone release (McLaughlin et al, 2014), attenuate behavioral responses to environmental threat (Aliczki et al, 2016), and reduce anxiety-like behaviors (Rubino et al, 2008b). Conversely, diminishing AEA signaling by overexpressing FAAH in the mPFC elicits a robust anxiogenic phenotype.…”

Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex as a Molecular Determinant of Pain and Ensuing Depression

“…However, some determinants, such as intractable somatic pain or psychological distress are essentially unavoidable. Long-term experiences of unavoidable, persistent distress would alter the prefrontal circuits that assess the internal state to decide coping strategies ( Roy et al, 2014 ; Shrestha et al, 2015 ; Aliczki et al, 2016 ; Zhang et al, 2017 ). It is well established that chronic pain, as well as depression, leads to hypodopaminergic tone in the brain ( Niikura et al, 2010 ; Belujon and Grace, 2017 ; Ong et al, 2018 ).…”