Dopamine and glucose, obesity, and reward deficiency syndrome

Abstract

Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain’s production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization of powerful dopamine D2 agonists have failed due to chronic down regulation of D2 receptors newer targets based on novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of reward deficiency.

Dopamine gene methylation patterns are associated with obesity markers and carbohydrate intake

“…Emerging evidences suggest that several genetic and epigenetic factors modulate the relationships between DA signaling, overconsumption, and obesity (Blum, Thanos, & Gold, 2014; Stice, Yokum, Zald, & Dagher, 2011). For instance, polymorphisms near or within key genes regulating dopaminergic synapse, including catechol‐o‐methyltransferase ( COMT ), D2 receptor ( DRD2 ), and DA active transporter ( DAT , SLC6A3 ) have been associated with altered reward circuitry responsivity related to a spectrum of addictive behaviors (Stice et al., 2011).…”

Effects of Ovariectomy and 17<i>β</i>-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight

“…Indeed, functional studies closely involved dopamine D2 receptors in several addiction patterns including sugar, alcohol, food and drugs [5] [6] [7] [8]. The D2 receptor existed as two alternatively spliced isoforms differing in the insertion of a stretch of 29 amino acids in the third intracellular loop [9].…”

The Effects of Different High-Protein Low-Carbohydrates Proprietary Foods on Blood Sugar in Healthy Subjects

“…Furthermore, the consumption of high-sugar snacks seems to be the main cause for the increase in intrahepatic triglyceride content (IHTG) 34 . Finally, the usual rapid and high glycemic peak caused by ultra-processed products, together with their lack in fiber, proteins and water, triggers an excessive consumption 19,35 .…”