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The dopamine motive system: implications for drug and food addiction

Key Points

  • The motivation to eat, like the motivation to take addictive drugs, activates the forebrain dopamine systems.

  • Excessive activation of this system strengthens the specific habits that precede the activation, sensitizing the animal's responsiveness to the specific conditions that elicit those habits.

  • At the same time, overactivation of the dopamine system downregulates the dopamine receptors, leaving the subject less interested in other activities.

  • The repeated intake of high-impact foods or addictive drugs thus makes food consumption or drug taking more habitual and decreases the importance of stimuli calling for alternatives.

  • Repeated drug use erodes the function of brain networks necessary for self-regulation, thereby facilitating impulsive, inflexible and compulsive actions.

Abstract

Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum. Cues that predict a reinforcing stimulus also modulate extrasynaptic dopamine concentrations, energizing motivation. Repeated administration of the reinforcer (drugs, energy-rich foods) generates conditioned associations between the reinforcer and the predicting cues, which is accompanied by downregulated dopaminergic response to other incentives and downregulated capacity for top-down self-regulation, facilitating the emergence of impulsive and compulsive responses to food or drug cues. Thus, dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding. Thus, interventions to rebalance the dopamine motive system might have therapeutic potential for obesity and addiction.

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Figure 1: Dopamine motive system.
Figure 2: Brain images of DA D2 receptor availability in individuals suffering from either cocaine use disorder or morbid obesity along with the images of matched controls.

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N.D.V.: researching data for article, substantial contribution to discussion of content, writing, review and editing of manuscript before submission. R.A.W.: researching data for article, substantial contribution to discussion of content, writing, review and editing of manuscript before submission. R.B.: substantial contribution to discussion of content, writing, review and editing of manuscript before submission.

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Correspondence to Nora D. Volkow.

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The authors declare that they have no pertinent competing financial interests or any other conflict of interest in relation to the work described herein.

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Influence of selected food-related signals on reward associated areas and behaviors (PDF 371 kb)

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Glossary

Obesity

Body weight that is above what is considered a healthy weight for a given height, normally ascertained through the screening tool referred to as the body mass index (BMI). Obesity (BMI >30) is associated with increased risk of illness, disability and death.

Relapse

Spontaneous recurrence or reinstatement of a learned behaviour after a given period of extinction, such as the reinstatement of compulsive drug use or the reinstatement of eating behaviours that lead to the reversal of diet-induced weight loss.

Addiction

A chronic brain disease associated with disruption of reward and motivation, memory and conditioning, executive and self-regulation, mood and stress neurocircuitry, the risk of which implicates environmental, genetic and social factors.

Reward

The subjective salience value of an object, stimulus or situation that has the potential to induce goal-oriented behaviour.

Motivation

A brain process triggered by intrinsic and/or extrinsic drivers that induce an animal or a person to move towards a goal.

Reinforcer

An event or stimulus that, once delivered, increases the probability of repeating the act that it follows; this term can apply to both food and drugs. Painful and aversive stimuli can also act as reinforcers but instead they increase the probability of avoiding the behaviours or circumstances that preceded the stimuli. Novel stimuli can also act as reinforcers by engaging attentional systems.

Tonic

Slow and gradual. Receptors activated by a tonic input typically adapt slowly throughout the stimulation period, conveying information about its duration.

Phasic

Sudden and transient, conveying information about sudden changes in stimulus intensity and rate and promoting rapid adaptation to the stimulus.

Striatum

A key region of the limbic system, dysfunctions of which have been associated with the pathophysiology of addiction and obesity.

Dorsal striatum

A region of the striatum associated with habits or stimulus–response learning.

Ventral tegmental area

(VTA). A cluster of midbrain neurons that sends dopaminergic projections to both limbic and cortical areas, thus playing a central role in reward-related and goal-directed behaviours. Note that while it has been traditionally believed that the VTA underlies reinforcement, recent optogenetic studies indicate that the SN also participates in this phenomenon.

Ventral striatum

A region of the striatum that contains the nucleus accumbens and is predominantly associated with reward and motivation.

Substantia nigra

(SN). A cluster of midbrain dopamine neurons that is predominantly associated with movement and involved in habit formation. More recent optogenetic studies also implicate it in reward functions.

Medium spiny neurons

A GABAergic striatal cell type of critical importance because of its pivotal roles not only in motor control, habituation and motivated behaviour but also in psychiatric disorders such as Parkinson disease, Huntington disease, schizophrenia and addiction.

Direct striatocortical pathway

Striatal pathway in which D1R-expressing (striatonigral projection) medium spiny neurons project from the striatum to the internal globus pallidum and the substantia nigra reticulata, which disinhibit thalamic excitatory neurons to the frontal cortex, facilitating movement.

Indirect striatocortical pathway

Striatal pathway in which D2R-expressing (striatopallidal projection) medium spiny neurons project from the striatum to the external globus pallidum and then to the subthalamic nucleus, which then projects into the internal pallidum and substantia nigra reticulata with a resultant inhibition of thalamic stimulation of the frontal cortex, inhibiting movement.

Heteromers

Receptors consisting of dimers and possibly higher-order entities with unique biochemical and functional characteristics, composed of different monomers from the same or different gene families.

Satiety

A feeling that follows food intake and that leads to meal termination. It is a complex psychological construct that can be linked to physicochemical measures related to stomach distention, blood levels of peptides such as cholecystokinin and glucagon-like peptide-1, peripheral biomarkers associated with meal termination, and neural activity related to sensory-stimulus-specific satiety.

Compulsive

Related to an uncontrollable, often unconscious urge to perform a specific act, often in a repetitive fashion.

Optogenetic stimulation and inhibition

A technique that allows the use of an external source of monochromatic light to stimulate or inhibit the activity of cells reversibly and with a high degree of spatiotemporal resolution (typically applied to selected neuronal populations that have been genetically modified to express light-sensitive ion channels).

Gut microbiome

The diverse collection of symbiotic microorganisms (flora) residing in the gastrointestinal tract that perform structural and histological functions and play significant roles in the regulation of host health maintenance and homeostasis.

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Volkow, N., Wise, R. & Baler, R. The dopamine motive system: implications for drug and food addiction. Nat Rev Neurosci 18, 741–752 (2017). https://doi.org/10.1038/nrn.2017.130

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