Trace Amine Associated Receptor 1 (TAAR1) Modulation of Food Reward

Abstract

Eating disorders and some forms of obesity are characterized by addictive-like, compulsive eating behavior which contains numerous similarities with compulsive drug use. Food intake is in part mediated by reward and reinforcement processes that can become dysregulated in these disorders. Additionally, impairments in inhibitory control regulation of reward-related responding can cause or further exacerbate binge and compulsive eating. Dysfunctions in two neurotransmitter systems in the mesocorticolimbic pathway, dopamine and glutamate, are thought to contribute to maladaptive eating behaviors. The trace amine associated receptor 1 (TAAR1) system is a promising therapeutic target for compulsive eating behavior due to the role of TAAR1 in synaptic transmission and in the modulation of dopaminergic and glutamatergic signaling. In support of this notion, the TAAR1 agonist RO5256390 was found to decrease the reinforcing effects of palatable food-cues and to reduce binge-like and compulsive-like eating of palatable food. Additionally, prolonged, intermittent access to palatable food was shown to downregulate TAAR1 in the prefrontal cortex, suggesting a potential role for TAAR1 signaling in inhibitory control processes. Research into the role of TAAR1 in addiction, including TAAR1’s ability to modulate psychostimulant reward and reinforcement, bolsters support for TAAR1 agonism as a pharmacological treatment for compulsive eating and other addictive behaviors. This review summarizes the evidence for TAAR1 agonism as a promising therapeutic for compulsive eating behavior as well as the hypothesized mechanism responsible for these effects.

Activation of trace amine‐associated receptor 1 selectively attenuates the reinforcing effects of morphine

“…In contrast, the TA 1 receptor full agonist RO5256390 reduced palatable food reward but not the consumption of a standard diet (Ferragud et al, 2017). Collectively, the effects of TA 1 receptor agonists on food reward and consumption might depend on various factors, for example, type of the particular TA 1 receptor agonist used (i.e., partial or full agonist), type of diet used in the experiment (i.e., standard diet or palatable food), and behavioural paradigm (Moore, Sabino, & Cottone, 2018). Despite these findings, we could not completely rule out the non-specific inhibition of RO5263397 in rats.…”

Trace Amines and Their Receptors

“…This distribution, along with the ease with which TAAR1 ligands are produced from dietary amino acids, makes TAAR1 an attractive putative molecular target for involvement in the control of energy metabolism and nutrient intake. Furthermore, the well documented beneficial effects of TAAR1 agonism in reducing addiction-associated compulsive behaviors mediated by the dopaminergic reward system raise the possibility that TAAR1 agonists may also be beneficial in controlling compulsive overeating, since food rewards are well established to be dopaminergic and/or glutamatergic in origin (Michaelides et al, 2012;Moore et al, 2018). Indeed, TAAR1 agonists have been reported to decrease food intake in diet-induced obese mice (Raab et al, 2015), resulting in weight loss and improved insulin sensitivity (Table 6).…”

Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

“…In the gut, it promotes motility, satiety, and eating behaviors. TAAR1 agonist decreased food intake and body weight in a diet-induced model of obesity with improved insulin sensitivity and plasma triglyceride levels [ 421 ]. Tyramine inhibited glycerol release by rat adipocytes enhanced fat deposition in epididymal white adipose tissue [ 422 ].…”