Hedonic Eating and the “Delicious Circle”: From Lipid-Derived Mediators to Brain Dopamine and Back

Abstract

Palatable food can be seductive and hedonic eating can become irresistible beyond hunger and negative consequences. This is witnessed by the subtle equilibrium between eating to provide energy intake for homeostatic functions, and reward-induced overeating. In recent years, considerable efforts have been devoted to study neural circuits, and to identify potential factors responsible for the derangement of homeostatic eating toward hedonic eating and addiction-like feeding behavior. Here, we examined recent literature on “old” and “new” players accountable for reward-induced overeating and possible liability to eating addiction. Thus, the role of midbrain dopamine is positioned at the intersection between selected hormonal signals involved in food reward information processing (namely, leptin, ghrelin, and insulin), and lipid-derived neural mediators such as endocannabinoids. The impact of high fat palatable food and dietary lipids on endocannabinoid formation is reviewed in its pathogenetic potential for the derangement of feeding homeostasis. Next, endocannabinoid signaling that regulates synaptic plasticity is discussed as a key mechanism acting both at hypothalamic and mesolimbic circuits, and affecting both dopamine function and interplay between leptin and ghrelin signaling. Outside the canonical hypothalamic feeding circuits involved in energy homeostasis and the notion of “feeding center,” we focused on lateral hypothalamus as neural substrate able to confront food-associated homeostatic information with food salience, motivation to eat, reward-seeking, and development of compulsive eating. Thus, the lateral hypothalamus-ventral tegmental area-nucleus accumbens neural circuitry is reexamined in order to interrogate the functional interplay between ghrelin, dopamine, orexin, and endocannabinoid signaling. We suggested a pivotal role for endocannabinoids in food reward processing within the lateral hypothalamus, and for orexin neurons to integrate endocrine signals with food reinforcement and hedonic eating. In addition, the role played by different stressors in the reinstatement of preference for palatable food and food-seeking behavior is also considered in the light of endocannabinoid production, activation of orexin receptors and disinhibition of dopamine neurons. Finally, type-1 cannabinoid receptor-dependent inhibition of GABA-ergic release and relapse to reward-associated stimuli is linked to ghrelin and orexin signaling in the lateral hypothalamus-ventral tegmental area-nucleus accumbens network to highlight its pathological potential for food addiction-like behavior.

Effects of a Fat-Rich Diet on the Spontaneous Release of Acetylcholine in the Neuromuscular Junction of Mice

“…This last situation has been described by Lalanza and co-authors [ 22 ], who observed that by suppressing a cafeteria diet in rats, an increase in their anxiety levels is caused. In this sense, it is known that the following diets based on tasty foods rich in fat can produce an addictive effect and its suppression generates a withdrawal syndrome that partly explains this increased anxiety [ 36 , 37 ].…”

The Modulating Role of Sex and Anabolic-Androgenic Steroid Hormones in Cannabinoid Sensitivity

“…As discussed above, brain CB1R distribution, synthesis of endogenous cannabinoids and activity of enzymes involved in cannabinoid metabolism (turnover) are significantly affected by sex hormones. At systems level, hormone-dependent differences and fluctuations in cannabinoid function may directly affect the activity of brain neurotransmitters and structures involved in cognitive and emotional aspects of motivated behaviors ( Schultz, 1997 ; Berridge and Robinson, 1998 ; Ikemoto and Panksepp, 1999 ; Salamone and Correa, 2002 ; Goto and Grace, 2005 ; Cheng and Feenstra, 2006 ; Di Chiara and Bassareo, 2007 ; Berridge et al, 2009 ), like feeding ( Melis et al, 2007 ; Bassareo et al, 2015 ; Fois et al, 2016 ; Coccurello and Maccarrone, 2018 ; Contini et al, 2018 ) and sexual behavior ( Pfaus et al, 1990 ; Pfaus and Everitt, 1995 ; Sanna et al, 2015 , 2017 ) as well as psychopathological states ( Dunlop and Nemeroff, 2007 ; Maia and Frank, 2017 ) and addiction-like behaviors ( Everitt and Robbins, 2005 , 2016 ). Such a modulation can happen (i) by a direct interaction of the cannabinoid system with the mesolimbic dopaminergic system, the core component of the neurobiological substrates at the basis of motivated behavior ( Gardner, 2005 ; Fadda et al, 2006 ; Lecca et al, 2006 ; Zangen et al, 2006 ; Melis and Pistis, 2007 ; Panagis et al, 2014 ; Bloomfield et al, 2016 ; Maldonado et al, 2006 ), or (ii) by indirect actions in limbic areas (e.g., hippocampus, amygdala, PFC) strictly interconnected with mesolimbic dopaminergic neurons through (mainly) glutamatergic projections to the ventral tegmental area and nucleus accumbens ( Laviolette and Grace, 2006 ; Laviolette, 2017 ).…”

Transcriptional regulation of the endocannabinoid system in a rat model of binge‐eating behavior reveals a selective modulation of the hypothalamic fatty acid amide hydrolase gene

“…Multiple neurotransmitter systems known to modulate homeostatic eating may contribute to BE behaviors, and so far a major focus has been placed on the role of dopaminergic and opioid systems (Avena & Bocarsly, 2012;Avena, Rada, & Hoebel, 2008;Bello, Yeh, Verpeut, & Walters, 2014;Mathes, Brownley, Mo, & Bulik, 2009). However, among endogenous systems, increasing evidence suggests that the endocannabinoid system (ECS) contributes to the modulation of energy balance by controlling food intake and hedonic eating as a negative feedback system that opposes anxiety (Coccurello & Maccarrone, 2018). The ECS is formed by endocannabinoids (eCBs), among which the two prototypes are the ethanolamine ("anandamide") and the glycerol ester (2-arachidonoylglycerol, 2-AG) of arachidonic acid, and their selective metabolic enzymes:…”