Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology

Abstract

Drugs and food exert their reinforcing effects in part by increasing dopamine (DA) in limbic regions, which has generated interest in understanding how drug abuse/addiction relates to obesity. Here, we integrate findings from positron emission tomography imaging studies on DA's role in drug abuse/addiction and in obesity and propose a common model for these two conditions. Both in abuse/addiction and in obesity, there is an enhanced value of one type of reinforcer (drugs and food, respectively) at the expense of other reinforcers, which is a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by drugs (abuse/addiction) and by large quantities of palatable food (obesity) in vulnerable individuals (i.e. genetic factors). In this model, during exposure to the reinforcer or to conditioned cues, the expected reward (processed by memory circuits) overactivates the reward and motivation circuits while inhibiting the cognitive control circuit, resulting in an inability to inhibit the drive to consume the drug or food despite attempts to do so. These neuronal circuits, which are modulated by DA, interact with one another so that disruption in one circuit can be buffered by another, which highlights the need of multiprong approaches in the treatment of addiction and obesity.

The role of dopamine in the pursuit of nutritional value

“…In animals and humans, obesity and intake of high-fat or high-sugar diets are associated with decreased dopamine D2 receptor expression and binding, decreased dopamine transporter function, and reduced thresholds for brain stimulation reward [91][92][93][94]. These changes may decrease the reward value of food, relative to control subjects, and this may drive people to overconsume to compensate.…”

Addictive Disorders in Nutritional Diseases ‐ From a Nutritional Viewpoint

“…Since all classes of misused drugs -alcohol, tobacco, stimulants, pain killers, tranquilizersare believed to usurp the naturally occurring reward pathways meant to help control food (and thus nutrient/energy) intake [1], substance addiction has the potential to induce clinical and subclinical malnutrition states. In addition, psychological desire for food is altered in individuals misusing substances.…”

“…Volkow et al [1] reviewed the similarities in neural circuitries underlying motivation to acquire and ingest food and drugs. Common neurotransmitters involved in these processes include mesolimbic dopamine and opioid circuits.…”

Epigenetic Mechanisms on Food Addiction

“…It has been recognized that the resemblance may reflect the involvement of the same neural systems, including those implicated in regulatory self-control and reward in both groups of disorders. It has been widely demonstrated that the DAergic "meso-limbic" reward system has a crucial role not only in the passage from an occasional use to an abuse of drugs, but also in the transition from a normal feeding to a maladaptive compulsive eating behavior [1,3,[6][7][8]. Human studies showed that DAergic release correlates with the reward from both drug and food use [9,10].…”

“…Genetic variants in eating disorders have been investigated [14][15][16], and the Taq1A (minor) allele of DA receptors D2 (DRD2) gene is associated with many of substance-misuse disorders [16][17][18]. Furthermore, it has been defined that lower levels of striatal DRD2s can signal a "reward-deficiency" state leading to over-seeking/ taking behaviors [7], thus suggesting that low DRD2 availability could be a formative genetic risk factor in compulsive food seeking/ taking behavior [3]. Finally, is conceivable that gene-environment interactions are able to induce neuroadaptations in several brain areas related to substance use disorders, such as the DAergic "meso-limbic" reward system.…”