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Cited by 525Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesEating Disorders and Behaviors

Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction

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Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., Baler, R.·2011·Current Topics in Behavioral Neurosciences
DOI 10.1007/7854_2011_169
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Abstract

Both drug addiction and obesity can be defined as disorders in which the saliency value of one type of reward (drugs and food, respectively) becomes abnormally enhanced relative to, and at the expense of others. This model is consistent with the fact that both drugs and food have powerful reinforcing effects-partly mediated by dopamine increases in the limbic system-that, under certain circumstances or in vulnerable individuals, could overwhelm the brain's homeostatic control mechanisms. Such parallels have generated significant interest in understanding the shared vulnerabilities and trajectories between addiction and obesity. Now, brain imaging discoveries have started to uncover common features between these two conditions and to delineate some of the overlapping brain circuits whose dysfunctions may explain stereotypic and related behavioral deficits in human subjects. These results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning (memory/learning), impulse control (behavioural inhibition), stress reactivity, and interoceptive awareness. Here, we integrate findings predominantly derived from positron emission tomography that shed light on the role of dopamine in drug addiction and in obesity, and propose an updated working model to help identify treatment strategies that may benefit both of these conditions.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes human PET and MRI imaging evidence that obesity and drug addiction share disruptions across overlapping brain circuits—reward/saliency, conditioning/habits, inhibitory control, motivation, interoception, and aversion/stress reactivity. It argues that reduced striatal D2 receptor signaling plus impaired prefrontal function underlies the loss of control over both drug and food intake.

Key findings

  • All addictive drugs increase dopamine in the nucleus accumbens, and drug-induced DA increases in striatum are proportional to the intensity of subjective euphoria or "high"; faster drug entry into the brain produces a more intense high at equivalent brain levels (cocaine smoked/i.v. vs. snorted).
  • Cocaine-addicted subjects showed markedly attenuated methylphenidate- or amphetamine-induced DA increases in striatum (50% lower in detoxified abusers and 80% in active abusers) and lower self-reported drug reward than controls, indicating that acute DA enhancement alone cannot explain compulsive use.
  • Conditioned cues raised DA in dorsal striatum and triggered craving in detoxified cocaine abusers; in these subjects cue-induced DA increases appeared larger than those produced by the stimulant drug itself.
  • Reduced striatal D2R availability was found in addicted subjects (persisting months after detoxification) and in obese individuals, where it was linked to decreased metabolic activity in OFC and ACC and to compulsive food intake in obese rodents; BMI correlated negatively with striatal D2R in obese and overweight individuals.
  • Obese individuals showed greater activation of reward/motivation regions (NAc, dorsal striatum, OFC, ACC, amygdala, hippocampus, insula) to high-calorie food pictures but less activation of reward circuits from actual food consumption than lean individuals, alongside greater somatosensory/palatability activation.
  • Medial habenula µ-opioid peptide binding was approximately 40% higher in rats that gained weight on a palatable diet than in those that did not.

Methods

  • Narrative review of human neuroimaging (PET with [11C]raclopride and [18F]FDG, fMRI, MRI morphometry, NMR spectroscopy) and preclinical studies comparing drug addiction and obesity; no new primary data were collected.
  • PET D2R studies rely on the fact that 85–90% of striatal D2R are unoccupied by endogenous DA at baseline, so drug- or cue-induced reductions in radiotracer binding index DA increases; most human work focuses on D2R because of the lack of specific radiotracers for D1, D3, D4, and D5 receptors.
  • Cited imaging samples include active cocaine-addicted subjects (n = 19) vs. controls (n = 24) for i.v. methylphenidate, cocaine-addicted subjects (n = 17) for cue exposure, and morbidly obese (n = 10) vs. control (n = 10) subjects for D2R availability.

Limitations

  • The paper states no formal limitations section; the text notes that most human studies focus on D2R due to the lack of specific radiotracers for D1, D3, D4, and D5 receptors, and that "some inconsistencies among studies" exist in the brain imaging data on executive-function regions and BMI.
  • Evident from the text: this is a narrative review without systematic search or meta-analysis, and many cited imaging studies use small samples (e.g., n = 10 per group in the obesity D2R comparison; n = 17 in the cue study).
  • Evident from the text: much of the mechanistic evidence (habenula, glutamatergic conditioning, D2R–compulsivity links) comes from rodent and non-human primate studies, and the proposed six-circuit working model is presented as a hypothesis rather than a tested causal account.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1007/7854_2011_169

Cites

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Statistics

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Claims the paper makes

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  • Premisecitation

    Other DA pathways, mesostriatal and mesocortical, also contribute to drug reward and addiction.

    “However, as described below, other DA pathways [mesostriatal (DA cells in substantia nigra projecting into dorsal striatum) and mesocortical (DA cells in VTA projecting into frontal cortex)] also contribute to drug reward and addiction (Wise 2009).”
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  • Premisecitation

    Homeostatic factors such as insulin, leptin, and ghrelin modulate food intake in part by increasing or decreasing the sensitivity of brain reward circuits to food stimuli.

    “Interestingly, there is growing evidence that homeostatic factors (e.g., insulin, leptin, ghrelin) modulate food intake in part by increasing or decreasing the sensitivity of brain reward circuits to food stimuli (Volkow et al 2011a).”
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    • cites Volkow et al 2011a

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  • Premisecitation

    The mesolimbic DA pathway, from DA cells in the ventral tegmental area projecting into the nucleus accumbens, seems to be crucial for drug reward.

    “The mesolimbic DA pathway [DA cells in ventral tegmental area (VTA) that project into the NAc] seems to be crucial for drug reward (Wise 2009).”
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    • cites Wise 2009 source

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  • Premisenone given

    In addiction, imaging studies have revealed that the disorder affects not only the DA reward circuit but also other DA pathways involved in conditioning/habits, motivation, and executive functions.

    “However, in the case of addiction, imaging studies have revealed that the disorder affects not only the DA reward circuit but also other DA pathways involved in the modulation of conditioning/habits, motivation, and executive functions (inhibitory control, salience attribution, and decision making), and that DA deficits may also participate in the enhanced stress reactivity and disruption of inter”
    Quote in the paperSubstantial claim
  • Premisereasoning

    DA deficits may participate in the enhanced stress reactivity and disruption of interoceptive awareness associated with addiction.

    “and that DA deficits may also participate in the enhanced stress reactivity and disruption of interoceptive awareness associated with addiction.”
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  • Classified as probably not a substantial claim. 5

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    Findingnone given

    Whether tested during early or protracted periods of abstinence/dieting, addicted/obese subjects show lower D2R in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (ACC and DLPFC), whose disruption results in compulsivity and impulsivity.

    “Also, whether tested during early or protracted periods of abstinence/dieting, addicted/obese subjects show lower D2R in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (ACC and DLPFC), whose disruption results in compulsivity and impulsivity.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Food cues, like drug cues, increase striatal extracellular DA and drive the motivation to engage in behaviors necessary to procure and eat food.

    “Food cues, like drug cues, increase striatal extracellular DA and drive the motivation to engage in the behaviors that are necessary to procure and eat the food, providing evidence for the involvement of DA not just in food reward but also in the non-hedonic motivational properties of food (i.e., caloric requirements) and in the decreases in inhibitory control seen in compulsive overeating (Avena”
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    • cites Volkow et al 2008a

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    Premisecitation

    Drugs of abuse, including alcohol, are consumed by humans or self-administered by laboratory animals because they are inherently rewarding, an effect mediated through DA-enhancing properties in the mesolimbic system.

    “Indeed, drugs of abuse (including alcohol) are consumed by humans or self-administered by laboratory animals because they are inherently rewarding, an effect that is mediated through its DA-enhancing properties in the mesolimbic system (Wise 2009).”
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    Premisecitation

    The response of VTA DA neurons to reward changes with repeated exposure: DA cells fire upon first exposure to a novel reward, but repeated exposure causes the neurons to stop firing upon reward consumption and fire instead when exposed to stimuli that predict the reward.

    “The response of VTA DA neurons to reward changes with repeated exposure.While DA cells fire upon first exposure to a novel reward, repeated exposure DA causes the neurons to stop firing upon reward consumption and fire instead when they are exposed to the stimuli that predict the reward (Schultz et al 1997), which is likely to underlie DA's role in conditioning.”
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    Premisecitation

    Brain imaging studies comparing DA increases induced by methylphenidate or amphetamine between cocaine addicted subjects and controls showed a marked attenuation of MP- or AMP-induced DA increases in striatum, 50% lower in detoxified abusers and 80% in active abusers, and lower self-reports of the drug's rewarding effects relative to non-drug-abusing controls.

    “Brain imaging studies that compare the DA increases induced by the stimulant drug methylphenidate (MP) or of amphetamine (AMP) between cocaine addicted subjects and controls showed a marked attenuation of MP or AMP induced DA increases in striatum (50% lower in detoxified abusers and 80% in active abusers) and lower self-reports of the drug's rewarding effects relative to non-drug-abusing controls”
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    • cites Martinez et al 2007 source

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    • cites Volkow et al 1997 source

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    Premisereasoning

    High calorie foods can promote over-eating and trigger learned associations between the stimulus and the reward.

    “High calorie foods can promote over-eating (eating that is uncoupled from energetic needs) and trigger learned associations between the stimulus and the reward (conditioning).”
    Quote in the paperSubstantial claim

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    Interpretationreasoning

    Drug-induced DA increases in the nucleus accumbens may be necessary for addiction, but they are insufficient to explain the impulsive and compulsive drug use characteristic of addiction because they also occur in nonaddicted individuals.

    “Such drug-induced DA increases in the NAc may be necessary for addiction, but the fact that they occur also in nonaddicted individuals indicates that they are insufficient to explain the impulsive and compulsive drug use characteristic of addiction.”
    Quote in the paperSubstantial claim

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    Premisecitation

    DA's role in reinforcement is more complex than just coding for reward per se, and stimuli that induce fast and large DA increases also trigger conditioned responses and elicit incentive motivation to procure them.

    “DA's role in reinforcement is more complex than just coding for reward per se (hedonic pleasure) and stimuli that induce fast and large DA increases also trigger conditioned responses and elicit incentive motivation to procure them (Owesson-White et al 2009).”
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    • cites Owesson-White et al 2009 source

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    Interpretationcitation

    These and related results support the notion that the hedonic response becomes deficient in drug addicted individuals, further strengthening the notion that the acute pharmacological DA-enhancing effects of the drug in the nucleus accumbens cannot by themselves explain the increased motivation to consume them.

    “These and related results (Volkow et al 2009a) support the notion that the hedonic response becomes deficient in drug addicted individuals, further strengthening then notion that the acute pharmacological DAenhancing effects of the drug in NAc cannot explain by themselves the increased motivation to consume them.”
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    • cites Volkow et al 2009a

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    Interpretationreasoning

    Comparable dopaminergic responses are linked with food reward, and these mechanisms are likely to play a role in excessive food consumption and obesity.

    “There is now evidence that comparable dopaminergic responses are linked with food reward and that these mechanisms are also likely to play a role in excessive food consumption and obesity.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Cocaine-associated cue exposure raises DA levels in the dorsal striatum and triggers a concomitant increase in the subjective experience of craving in detoxified cocaine abusers.

    “This hypothesis is consistent with independent observations (Volkow et al 2006b;Wong et al 2006) that show the power of cocaine-associated cue exposure to raise DA levels in the dorsal striatum and trigger a concomitant increase in the subjective experience of craving in detoxified cocaine abusers (Fig. 5).”
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    • cites Volkow et al 2006b

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    Premisecitation

    In the striatum, D2Rs mediate signaling from the striatal indirect pathway that modulates prefrontal regions, and downregulation of D2Rs in animal models has been shown to enhance sensitization to the effects of drugs.

    “In the striatum D2Rs mediate signaling from the striatal indirect pathway that modulates prefrontal regions, and its downregulation in animal models has been shown to enhance sensitization to the effects of drugs (Ferguson et al 2011).”
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    • cites Ferguson et al 2011 source

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    Premisecitation

    When non-obese male subjects were asked to inhibit their craving for food while being exposed to food cues, they exhibited decreased metabolic activity in amygdala and OFC, as well as in hippocampus, insula and striatum, and decreases in OFC were associated with reductions in food craving.

    “Indeed, imaging studies showed that when non-obese male subjects were asked to inhibit their craving for food while being exposed to food cues, they exhibited decreased metabolic activity in amygdala and OFC (as well as in hippocampus), insula and striatum; and that the decreases in OFC were associated with reductions in food craving (Wang et al 2009).”
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    • cites Wang et al 2009 source

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    Interpretationcitation

    This suggests a dynamic interaction between the amount of food eaten, reflected in part in BMI, and the reactivity of reward regions to high-calorie food, reflected in activation of OFC and ACC, in normal-weight individuals, which is lost in obesity.

    “This suggests a dynamic interaction between the amount of food eaten (reflected in part in the BMI) and the reactivity of reward regions to high-calorie food (reflected in the activation of OFC and ACC) in normalweight individuals, which is lost in obesity.”
    Quote in the paperSubstantial claim

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    Premisecitation

    A study in subjects at high risk for alcoholism who were not alcoholics revealed a higher than normal striatal D2R availability that was associated with normal metabolism in OFC, ACC, and DLPFC.

    “Indeed, a study done in subjects who, despite having a high risk for alcoholism (positive family history of alcoholism) were not alcoholics, revealed a higher than normal striatal D2R availability that was associated with normal metabolism in OFC, ACC, and DLPFC (Volkow et al 2006a).”
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    • cites Volkow et al 2006a

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    Interpretationcitation

    In subjects at risk for alcoholism, normal prefrontal function was linked to enhanced striatal D2R signaling, which in turn may have protected them from alcohol abuse.

    “This suggests that in these subjects at risk for alcoholism the normal prefrontal function was linked to enhanced striatal D2R signaling, which in turn may have protected them from alcohol abuse.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning

    Given that dysfunction in OFC and ACC results in compulsivity, this might be part of the mechanism by which low striatal D2R signaling facilitates hyperphagia.

    “Given that dysfunction in OFC and ACC results in compulsivity [see review (Fineberg et al 2009)], this might be part of the mechanism by which low striatal D2R signaling facilitates hyperphagia (Davis et al 2009).”
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    Interpretationcitation

    Enhanced activity of regions that process palatability could make obese subjects favor food over other natural reinforcers, whereas decreased activation of dopaminergic targets by actual food consumption might lead to overconsumption as a means to compensate for weak D2R-mediated signaling.

    “An enhanced activity of regions that process palatability could make obese subjects favor food over other natural reinforcers, whereas decreased activation of dopaminergic targets by the actual food consumption might lead to overconsumption as a means to compensate for weak D2R-mediated signaling (Stice et al 2008a).”
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    • cites Stice et al 2008a

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    Premisecitation

    Obese individuals exhibited less activation of reward circuits from actual food consumption than lean individuals, whereas they showed greater activation of somatosensory cortical regions that process palatability when they anticipated consumption.

    “Surprisingly, obese individuals exhibited less activation of reward circuits from actual food consumption (consummatory food reward) than lean individuals, whereas they showed greater activation of somatosensory cortical regions that process palatability when they anticipated consumption (Stice et al 2008b).”
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    • cites Stice et al 2008b

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    Premisecitation

    Both preclinical and clinical studies have provided evidence of decreased striatal D2R signaling in obesity, which is linked with reward in the NAc but also with the establishment of habits and routines in the dorsal striatum.

    “Both preclinical and clinical studies have provided evidence of decreased striatal D2R signaling, which, as mentioned above, is linked with reward (NAc) but also with the establishment of habits and routines (dorsal striatum) in obesity (Geiger et al 2009;Wang et al 2001).”
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    • cites Geiger et al 2009 source

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    Premisecitation

    Decreased striatal D2R availability has been linked to compulsive food intake in obese rodents and with decreased metabolic activity in OFC and ACC in obese humans.

    “Importantly, decreased striatal D2R availability has been linked to compulsive food intake in obese rodents (Johnson and Kenny 2010) and with decreased metabolic activity in OFC and ACC in obese humans (Volkow et al 2008b) (Fig. 7 a-c).”
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    • cites Volkow et al 2008b

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    Interpretationcitation

    Since decreased D2R-related signaling is also likely to reduce sensitivity to other natural rewards, this deficit in obese individuals might also contribute to compensatory overeating.

    “In addition, since decreased D2R-related signaling is also likely to reduce the sensitivity to other natural rewards, this deficit in obese individuals might also contribute to compensatory overeating (Geiger et al 2008).”
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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    The prefrontal cortex plays a crucial role in executive function, including inhibitory control.

    “The prefrontal cortex (PFC) plays a crucial role in executive function, including inhibitory control.”
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    Interpretationreasoning

    These executive processes are modulated by D1R and D2R, presumably also D4R, and thus decreased activity in PFC, both in addiction and in obesity, is likely to contribute to poor control and compulsivity.

    “These processes are modulated by D1R and D2R (presumably also D4R) and thus the decreased activity in PFC, both in addiction and in obesity, is likely to contribute to poor control and compulsivity.”
    Quote in the paperNot a substantial claim

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    Interpretationcitation

    This suggests that activation of these prefrontal regions with drug exposure may be specific to addiction and associated with the enhanced desire for the drug.

    “This suggests that the activation of these prefrontal regions with drug exposure may be specific to addiction and associated with the enhanced desire for the drug.”
    Quote in the paperSubstantial claim

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    Premisecitation

    When responses to intravenous methylphenidate are compared between cocaine addicted and non-addicted individuals, the former responded with increased metabolism in ventral ACC and medial OFC, an effect associated with craving, while the latter showed the opposite response, namely decreased metabolism in these regions.

    “Moreover, it is possible to demonstrate that when the responses to i.v.MP are compared between cocaine addicted and non-addicted individuals, the former responded with increased metabolism in ventral ACC and medial OFC (an effect associated with craving), while the latter showed the opposite response, namely decreased metabolism in these regions (Volkow et al 2005).”
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    • cites Volkow et al 2005

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    Premisecitation

    Dopaminergic signaling modulates motivation; behavioral traits such as vigor, persistence, and investing continued effort toward achieving a goal are subject to modulation by DA acting through several target regions, including NAc, ACC, OFC, DLPFC, amygdala, dorsal striatum, and ventral pallidum.

    “Dopaminergic signaling also modulates motivation.Behavioral traits such as vigor, persistence, and investing a continued effort toward achieving a goal, are all subject to modulation by DA acting through several target regions, including NAc, ACC, OFC, DLPFC, amygdala, dorsal striatum, and ventral pallidum (Salamone et al 2007).”
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    Premisecitation

    Delay discounting seems to depend on the function of ventral striatum and of the PFC, including OFC, and is sensitive to DA manipulations.

    “Delay discounting seems to depend on the function of ventral striatum (Gregorios-Pippas et al 2009) and of the PFC, including OFC (Bjork et al 2009), and is sensitive to DA manipulations (Pine et al 2010).”
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    Premisecitation

    Because drug taking becomes the main motivational drive in drug addiction, addicted subjects are aroused and motivated by the process of obtaining the drug but tend to become withdrawn and apathetic when exposed to non-drug-related activities.

    “Because drug taking becomes the main motivational drive in drug addiction (Volkow et al 2003), addicted subjects are aroused and motivated by the process of obtaining the drug but tend to become withdrawn and apathetic when exposed to non-drug-related activities.”
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    • cites Volkow et al 2003 source

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    Premisecitation

    The OFC plays a role in learning stimulus-reinforcement associations and conditioning, supports conditioned-cue elicited feeding, and probably contributes to overeating irrespective of hunger signals.

    “The OFC plays a role in learning stimulus-reinforcement associations and conditioning (Cox et al 2005;Gallagher et al 1999), supports conditioned-cue elicited feeding (Weingarten 1983), and probably contributes to overeating irrespective of hunger signals (Ogden and Wardle 1990).”
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    Premisecitation

    In contrast to the decreases in prefrontal activity reported in detoxified cocaine abusers when not stimulated with drug or drug cues, these prefrontal regions become activated when cocaine abusers are exposed to craving-inducing stimuli, either drugs or cues.

    “In contrast to the decreases in prefrontal activity reported in detoxified cocaine abusers when not stimulated with drug or drug cues [see review (Volkow et al 2009a)], these prefrontal regions become activated when cocaine abusers are exposed to craving-inducing stimuli (either drugs or cues) (Grant et al 1996;Volkow et al 1999a;Wang et al 1999).”
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    • cites Grant et al 1996 source

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    • cites Volkow et al 1999a

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    Premisecitation

    Cocaine abusers, studied shortly after an episode of cocaine binging, showed an increase in metabolic activity in OFC and ACC, also dorsal striatum, that was associated with craving.

    “This result is reminiscent of the observation that cocaine abusers, studied shortly after an episode of cocaine binging, showed an increase in metabolic activity in OFC and ACC (also dorsal striatum) that was associated with craving (Volkow et al 1991).”
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    • cites Volkow et al 1991 source

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    Interpretationreasoning

    The enhanced OFC activation by food stimulation is likely to reflect downstream dopaminergic effects and participate in DA's involvement in the drive for food consumption.

    “The enhanced OFC activation by the food stimulation is likely to reflect downstream dopaminergic effects and participate in DA's involvement in the drive for food consumption.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The reactivity of the insula has been suggested to serve as a biomarker to help predict relapse.

    “Accordingly, the reactivity of this brain region has been suggested to serve as a biomarker to help predict relapse (Janes et al 2010).”
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    • cites Janes et al 2010 source

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    Interpretationcitation

    Cortical areas such as the DLPFC and OFC that are involved in inhibitory control have been found to become activated in successful dieters in response to meal consumption, suggesting a potential target for behavioral retraining in the treatment of obesity and also in addiction.

    “Interestingly, cortical areas, like the DPFC and OFC that are involved in inhibitory control, have also been found to become activated in successful dieters in response to meal consumption (DelParigi et al 2007), suggesting a potential target for behavioral retraining in the treatment of obesity (and also in addiction).”
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    • cites DelParigi et al 2007 source

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    Premisecitation

    The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions and appears to have an interoceptive function, integrating autonomic and visceral information with emotion and motivation, thus providing conscious awareness of urges.

    “The insula, particularly its more anterior regions, is reciprocally connected to several limbic regions (e.g., ventromedial prefrontal cortex, amygdala, and ventral striatum) and appears to have an interoceptive function, integrating the autonomic and visceral information with emotion and motivation, thus providing conscious awareness of these urges (Naqvi and Bechara 2009).”
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    • cites Naqvi and Bechara 2009 source

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    Premisecitation

    Using PET to measure brain glucose metabolism in healthy controls, the authors reported a negative correlation between BMI and metabolic activity in DLPFC, OFC and ACC; metabolic activity in prefrontal regions predicted the subjects' performance in tests of executive function.

    “Using PET to measure brain glucose metabolism in healthy controls, we reported a negative correlation between BMI and metabolic activity in DLPFC, OFC and ACC.In this study, the metabolic activity in prefrontal regions predicted the subjects' performance in tests of executive function (Volkow et al 2009c).”
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    • cites Volkow et al 2009c

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    Premisecitation

    Another study found no differences in gray matter volumes between obese and lean subjects, but recorded a positive correlation between white matter volume in basal brain structures and waist to hip ratios, a trend partially reversed by dieting.

    “Another study, found no differences in gray matter volumes between obese and lean subjects, however, it did record a positive correlation between white matter volume in basal brain structures and waist to hip ratios; a trend that was partially reversed by dieting (Haltia et al 2007b).”
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    • cites Haltia et al 2007b

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    Premisecitation

    An MRI study in elderly women using voxel-wise morphometry found a negative correlation between BMI and gray matter volumes, including frontal regions, which in the OFC was associated with impaired executive function.

    “For example, an MRI study done in elderly women, using voxel-wise morphometry, found a negative correlation between BMI and gray matter volumes (including frontal regions), which, in the OFC, was associated with impaired executive function (Walther et al 2010).”
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    Premisecitation

    The insula is a primary gustatory area that participates in many aspects of eating behavior, such as taste; the rostral insula provides information to the OFC to influence its multimodal representation of the pleasantness or reward value of incoming food.

    “The insula is also a primary gustatory area, which participates in many aspects of eating behavior, such as taste.In addition, the rostral insula (connected to primary taste cortex) provides information to the OFC to influence its multimodal representation of the pleasantness or reward value of incoming food (Rolls 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rolls 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    DA signaling may also be necessary for sensing the calorie content of food; when normal weight women tasted a sweetener with calories, sucrose, both the insula and dopaminergic midbrain areas became activated, whereas tasting a calorie-free sweetener, sucralose, only activated the insula.

    “However, the DA signaling may also be necessary for sensing the calorie content of food.For example, when normal weight women tasted a sweetener with calories (sucrose), both the insula and dopaminergic midbrain areas became activated, whereas tasting a calorie-free sweetener (sucralose) only activated the insula (Frank et al 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Frank et al 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Gastric distention results in activation of the posterior insula, which is likely to reflect its role in the awareness of body states, in this case of fullness.

    “Indeed, gastric distention results in activation of the posterior insula, which is likely to reflect its role in the awareness of body states (in this case of fullness) (Wang et al 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wang et al 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A highly palatable food diet can induce obesity in rats, with the weight increases correlating with increases in μ-opioid peptide binding in the basolateral and basomedial amygdala.

    “A highly palatable food diet can induce obesity in rats, with the weight increases correlating with increases in µ-opioid peptide binding in the basolateral and basomedial amygdala.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Smith et al 2002 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the case of nicotine, the α5 nicotinic receptors in the habenula appear to modulate the aversive responses to large doses of nicotine, and the α5 and α2 receptors in the habenula are implicated in nicotine withdrawal.

    “In the case of nicotine, the α5 nicotinic receptors in the habenula appear to modulate the aversive responses to large doses of nicotine (Fowler et al 2011) and the α5 and α2 receptors in the habenula are implicated in nicotine withdrawal (Salas et al 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Fowler et al 2011 source

      Not checked in the free run.

    • cites Salas et al 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Neurons in the rostromedial tegmental nucleus, which receive a major input from the lateral habenula, project to VTA DA neurons and are activated after food deprivation.

    “neurons in the rostromedial tegmental nucleus, which receive a major input from the lateral habenula, project to VTA DA neurons and are activated after food deprivation (Jhou et al 2009)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jhou et al 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    As a consequence of the sequential disruption in these circuits, individuals may experience an enhanced motivational value of the drug/food (secondary to learned associations through conditioning and habits) at the expense of other reinforcers (secondary to decreased sensitivity of the reward circuit).

    “As a consequence of the sequential disruption in these circuits, individuals may experience 1) an enhanced motivational value of the drug/food (secondary to learned associations through conditioning and habits) at the expense of other reinforcers (secondary to decreased sensitivity of the reward circuit)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The ability to resist the urge to use a drug or eat past the point of satiety requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from ingesting the food/drug and the desire to ingest the food/drug.

  • May combine two claims.

    Premisecitation

    Subjects who have recovered from anorexia nervosa show less activation in the insula when tasting sucrose and no association of feelings of pleasantness with insular activation as observed in the normal controls.

    “In contrast, subjects who have recovered from anorexia nervosa show less activation in the insula when tasting sucrose and no association of feelings of pleasantness with insular activation as observed in the normal controls (Wagner et al 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wagner et al 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Hyperphagia could result from a drive to compensate for a weakened reward circuit (processed through dopamine regulated corticostriatal circuits) combined with a heightened sensitivity to palatability (hedonic properties of food processed in part through the somatosensory cortex).

    “Hyperphagia could result from a drive to compensate for a weakened reward circuit (processed through dopamine regulated corticostriatal circuits) combined with a heightened sensitivity to palatability (hedonic properties of food processed in part through the somatosensory cortex).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Nicotine seems to activate VTA dopamine neurons directly via stimulation of nicotinic cholinergic receptors on those neurons and indirectly via stimulation of its receptors on glutamatergic nerve terminals that innervate the dopamine cells.

    “Nicotine seems to activate VTA dopamine neurons directly via stimulation of nicotinic cholinergic receptors on those neurons and indirectly via stimulation of its receptors on glutamatergic nerve terminals that innervate the dopamine cells.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nestler 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is some evidence that nicotine and alcohol may activate endogenous opioid pathways and that these and other drugs of abuse may activate endogenous cannabinoid pathways.

    “Finally, there is some evidence that nicotine and alcohol may activate endogenous opioid pathways and that these and other drugs of abuse (such as opiates) may activate endogenous cannabinoid pathways (not shown).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nestler 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    These circuits also interact with circuits involved in mood regulation, including stress reactivity (which involves the amygdala, hypothalamus, habenula) and interoception (which involves the insula and ACC and contributes to awareness of craving).

    “These circuits also interact with circuits involved in mood regulation, including stress reactivity (which involves the amygdala, hypothalamus, habenula) and interoception (which involves the insula and ACC and contributes to awareness of craving).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    When these circuits are balanced, this results in proper inhibitory control and decision making.

    “When these circuits are balanced, this results in proper inhibitory control and decision making.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The ability to resist the urge to use a drug or eat past the point of satiety requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from ingesting the food/drug and the desire to ingest the food/drug.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Phencyclidine (PCP) may act by inhibiting postsynaptic NMDA glutamate receptors in the NAc.

    “Phencyclidine (PCP) may act by inhibiting postsynaptic NMDA glutamate receptors in the NAc.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nestler 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Opiates also directly act on opioid receptors on NAc neurons, and opioid receptors, like D2 dopamine receptors, signal via Gi; hence, the two mechanisms converge within some NAc neurons.

    “Opiates also directly act on opioid receptors on NAc neurons, and opioid receptors, like D 2 dopamine (DA) receptors, signal via G i ; hence, the two mechanisms converge within some NAc neurons.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Nestler 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cocaine abusers show both decreases in baseline striatal D2R availability and decreases in DA release when given i.v. MP.

    “Note that cocaine abusers show both decreases in baseline striatal D2R availability (placebo measure) and decrases in DA release when given i.v.MP (measured as decreases in D2R availability from baseline).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Volkow et al 1997 source

      Not checked in the free run.

    • cites Wang et al 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cannabinoid mechanisms involve activation of CB1 receptors on glutamatergic and GABAergic nerve terminals in the NAc, and on NAc neurons themselves.

    “Cannabinoid mechanisms seem complex, and they involve activation of CB1 receptors (which, like D2 and opioid receptors, are Gi linked) on glutamatergic and GABAergic nerve terminals in the NAc, and on NAc neurons themselves.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nestler 2005 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    During addiction, when the enhanced expectation value of the drug in the reward, motivation, and memory circuits overcomes the control circuit, this favors a positive-feedback loop initiated by the consumption of the drug and perpetuated by the enhanced activation of the motivation/drive and memory circuits.

    “During addiction, when the enhanced expectation value of the drug in the reward, motivation, and memory circuits overcomes the control circuit, this favors a positive-feedback loop initiated by the consumption of the drug and perpetuated by the enhanced activation of the motivation/drive and memory circuits.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The ability to resist the urge to use a drug or eat past the point of satiety requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from ingesting the food/drug and the desire to ingest the food/drug.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Several neurotransmitters are implicated in these neuroadaptations, including glutamate, GABA, norepinephrine, corticotropicreleasing factor, and opioid receptors.

    “Several neurotransmitters are implicated in these neuroadaptations, including glutamate, GABA, norepinephrine, corticotropicreleasing factor, and opioid receptors.”
    Quote in the paperNot a substantial claim
58 of 58

  • The paper relies on this without support.

    The ability to resist the urge to use a drug or eat past the point of satiety requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from ingesting the food/drug and the desire to ingest the food/drug.

    “The ability to resist the urge to use a drug or eat past the point of satiety requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from ingesting the food/drug and the desire to ingest the food/drug.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Disruption of the DA reward circuit has been implicated in loss of control in both addiction and obesity, although the physiological mechanisms that disrupt DA striatal circuits diverge.

    “Disruption of the DA reward circuit has been implicated in the loss of control seen in both addiction and obesity (2), although the physiological mechanisms that disrupt the function of the DA striatal circuits, including those implicated in reward (ventral striatum) and in habit formation (dorsal striatum), present clear divergences (3).”

    From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [2]

  • There are several identifiable circuits in the brain whose dysfunctions uncover real and clinically meaningful parallels between obesity and drug addiction.

    “Whether or not certain types of obesity should be defined as behavioural addictions (160), there are several identifiable circuits in the brain (2), whose dysfunctions uncover real and clinically meaningful parallels between the two disorders.”

    From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [2]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Human imaging study cited as preclinical evidence

    Minor

    The cited Stoeckel et al. study is described in the reference list as brain imaging of obese women viewing food pictures, contradicting its characterization here as preclinical evidence about VTA dopamine activity and food consumption.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Wang GJ, Volkow N, Telang F, Logan J, Wong C, Jayne M et al (2010) Decreased brain dopaminergic responses in active cocaine dependent subjects. J Nucl Med 51:269

Cited by

Sorted by citations

Related

Authors
Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., & Baler, R.
Affiliations
  • National Institute on Drug Abuse (US)
  • Brookhaven National Laboratory (US)
  • National Institutes of Health (US)
Corresponding author
Volkow, N. D.
ORCID
Venue
Current Topics in Behavioral Neurosciences
Publisher
Springer Berlin Heidelberg
Published
2011
Volume
11
Pages
1-24
ISSN
  • 1866-3370 (ISSN-L)
  • 1866-3389
DOI
10.1007/7854_2011_169
OpenAlex
W2116454997
Semantic Scholar
55e194af4541f1baa617b15e4c65397cd2494550
Cited by
525
References
127
Citations by year
2026: 11 · 2025: 19 · 2024: 22 · 2023: 30 · 2022: 31 · 2021: 41 · 2020: 77 · 2019: 32 · 2018: 37 · 2017: 50 · 2016: 36 · 2015: 39 · 2014: 47 · 2013: 33 · 2012: 20
FWCI
30.07
Type
book chapter
Language
en
Open access
Licence
Locations
  • Current topics in behavioral neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • University of North Texas Digital Library (University of North Texas) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
Keywords
food reward, drug addiction, obesity, reward salience, dopamine, dopaminergic pathways, incentive motivation, impulse control, stress reactivity, interoceptive awareness, positron emission tomography, treatment options
MeSH terms
Animals, Brain, Dopamine, Food, Humans, Neural Pathways, Obesity, Reward, Substance-Related Disorders, Positron-Emission Tomography

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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