Impaired brain endocannabinoid tone in the activity‐based model of anorexia nervosa

Abstract

Objective Despite the growing knowledge on the functional relationship between an altered endocannabinoid (eCB) system and development of anorexia nervosa (AN), to date no studies have investigated the central eCB tone in the activity‐based anorexia (ABA) model that reproduces key aspects of human AN. Method We measured levels of two major eCBs, anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG), those of two eCB‐related lipids, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), and the cannabinoid type‐1 receptor (CB1R) density in the brain of female ABA rats, focusing on areas involved in homeostatic and rewarding‐related regulation of feeding behavior (i.e., prefrontal cortex, nucleus accumbens, caudato putamen, amygdala, hippocampus and hypothalamus). Analysis was carried out also at the end of recovery from the ABA condition. Results At the end of the ABA induction phase, 2‐AG was significantly decreased in ABA rats in different brain areas but not in the caudato putamen. No changes were detected in AEA levels in any region, whereas the levels of OEA and PEA were decreased exclusively in the hippocampus and hypothalamus. Furthermore, CB1R density was decreased in the dentate gyrus of hippocampus and in the lateral hypothalamus. After recovery, both 2‐AG levels and CB1R density were partially normalized in some areas. In contrast, AEA levels became markedly reduced in all the analyzed areas. Discussion These data demonstrate an altered brain eCB tone in ABA rats, further supporting the involvement of an impaired eCB system in AN pathophysiology that may contribute to the maintenance of some symptomatic aspects of the disease.

Epigenetic regulation of the cannabinoid receptor CB1 in an activity‐based rat model of anorexia nervosa

“…Overall, the reduction of Cnr1 expression in the Hyp might be a partial loss of need to restore energy homeostasis, whereas the down‐regulation in the NAc could be linked to anhedonia, which might occur during the development of the phenotype. In our previous mentioned paper (Collu et al, 2019) with regard to CB1 receptors, we found a significantly decreased receptor density in the lateral Hyp and in the dental gyrus of the hippocampus of ABA rats while only a trend in the PFC.…”

“…Very recently, we have found 2‐AG levels significantly decreased in several brain area of ABA rats after the induction phase (Collu et al, 2019), this reduction of the eCB tone could be responsible for the development of altered feeding behaviors (Wu, Clark, & Palmiter, 2012) and cognitive and emotional alterations (Nestler & Carlezon Jr., 2006), all hallmarks in AN (Koch, 2017).…”

Endocannabinoid System Components as Potential Biomarkers in Psychiatry

“…2-AG significantly decreased in various brain areas but not in the caudate putamen, whereas no changes were observed in AEA. Density of CB1r was reduced in the dentate gyrus of Hipp and in the lateral Hyp (369). These results suggested that ECS is involved in the contribution and maintenance of some aspects in the pathophysiology of AN.…”

The association of dietary patterns with endocannabinoids levels in overweight and obese women

“…In the past 15 years, the endocannabinoid system (ECS) has appeared as a lipid signaling system involved in the energy balance regulation, as it has control on every aspect of calorie regulation [6]. This system consists of endogenous ligands N-arachidonoylethanolamide (anandamide), 2-arachidonoyl glycerol (2 AG), the cannabinoid 1 and 2 receptors, and enzymes responsible for the biosynthesis and degradation of ligands [7]. The endogenous ligands are lipid derivatives of a ω 6polyunsaturated fatty acid, arachidonic acid (ARA), with multiple functions [8].…”