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.

Figure 1

(a) Images of DA D₂ receptors (measured with [¹¹C]raclopride in striatum) in (i) a control and (ii) a cocaine abuser. (b) Diagram showing where glucose metabolism was associated with DA D₂ receptors in cocaine abusers, which included the orbitofrontal cortex (OFC), the cingulate gyrus (CG) and the dorsolateral prefrontal cortex (PreF). (c) Regression slopes between D₂ receptor availability and brain glucose metabolism in OFC in a group of detoxified (i) cocaine and (ii) methamphetamine abusers. Modified from Volkow et al. (2007b).

Figure 2

(a) Averaged images for DA D₂ receptors (measured with [¹¹C]raclopride) in a group of (i) controls (n=10) and (ii) morbidly obese subjects (n=10). (b) Results from SPM identifying the areas in the brain where D₂ receptors availability was associated with brain glucose metabolism; these included the OFC, the CG and the DLPFC (region not shown in sagittal plane). (c) Regression slopes between D₂ receptor availability (measured in striatum) and brain glucose metabolism in (i) CG and (ii) OFC in obese subjects. Modified from Wang et al. (2001) and Volkow et al. (in press).

Figure 3

(a) Averaged images of DA D₂ receptors (measured with [¹¹C]raclopride) in a group of cocaine-addicted subjects (n=16) tested while viewing a neutral video and while viewing a cocaine-cue video. (b) Histogram showing the measures of DA D₂ receptor availability (B_max/K_d) in caudate and putamen when viewing the neutral (blue bars) and cocaine-cue (red bars) videos. (c) Regression slopes between DA changes (assessed as changes in B_max/K_d) induced by the cocaine video and the self-reports of craving. Modified from Volkow et al. (2006b).

Figure 4

(a) Averaged images of DA D₂ receptors (measured with [¹¹C]raclopride) in a group of controls (n=10) tested while reporting on their family genealogy (neutral stimuli) or while being exposed to food. (b) Histogram showing the measures of DA D₂ receptor availability (B_max/K_d) in striatum (average caudate and putamen) when viewing the neutral and cocaine-cue videos. (c) Regression slopes between DA changes (assessed as changes in B_max/K_d) induced by the food stimuli and the self-reports of desire for the food. ^aTo enhance the DA signal, subjects were pretreated with oral MP to block DA transporters and so amplify the DA signal. Modified from Volkow et al. (2002b).

Figure 5

Model of brain circuits involved with addiction and obesity: reward/saliency motivation/drive, memory/conditioning and inhibitory control/emotional regulations. Disrupted activity in brain regions involved with inhibitory control/emotional regulation when coupled with enhanced activation of reward/saliency and memory/conditioning leads to enhanced activation of the motivational/drive circuit and the resultant compulsive behaviour (drug taking or food ingestion) when the individual is exposed to the reinforcer (drug or food), conditioned cues or a stressor. Note that circuits that regulate mood as well as internal awareness (interoception) are also likely to modulate the ability to exert control over incentive drives. (a) Healthy brain, (b) dysregulated brain. Modified from Volkow et al. (2003b).