Obesity and addiction: neurobiological overlaps

In the paper

“findings of attenuated responses to drug rewards in animal models of obesity (33,34).”

What the sources say

• Supported

  The Results section ('Exposure to dietary fat attenuates amphetamine conditioned place preference'; page not provided) reports that obese high-fat-fed rats did not develop a preference for the amphetamine-paired compartment, unlike chow-fed rats. The same reduced response occurred in high-fat-fed rats that were not obese, so the study does not isolate obesity as its cause. (LLM, conf=0.90)

  cites [33] Davis JF Tracy AL Schurdak JD Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat Behav Neurosci 2008 122 1257 1263 19045945 PMC2597276 source
• Partly supported

  The Abstract reports diminished acquisition of cocaine self-administration in high-fat-fed rats, suggesting reduced cocaine reinforcement. It also states that the effect was not a function of diet-induced obesity. The source therefore supports an attenuated response to cocaine in high-fat-fed rats, but not the broader attribution to obesity or drug rewards generally. (LLM, conf=0.88)

  cites [34] Wellman PJ Nation JR Davis KW Impairment of acquisition of cocaine self-administration in rats maintained on a high-fat diet Pharmacol Biochem Behav 2007 88 89 93 17764729 PMC2094387 sourceExperimental — accuracy not yet measured

In the paper

“The OFC plays a role in learning stimulus-reinforcement associations and conditioning (118,119), supports conditioned-cue-elicited feeding (120) and probably contributes to overeating irrespective of hunger signals (121).”

What the sources say

• Supported

  The Discussion reports OFC responses to stimuli that acquired affective value through associative conditioning and links the OFC to representing their value after conditioned-stimulus–reward pairings. This supports the attributed role in stimulus–reinforcement associations and conditioning. (LLM, conf=0.88)

  cites [118] Cox SM Andrade A Johnsrude IS Learning to like: a role for human orbitofrontal cortex in conditioned reward J Neurosci 2005 25 2733 2740 15758183 PMC6725165 source
• Supported

  The Discussion describes OFC as important for associative information linking cues to the value of reinforcers. The Abstract reports that OFC lesions altered conditioned responding after reinforcer devaluation, while leaving initial acquisition of the conditioned response intact; this supports a role in conditioning without implying OFC is required for initial learning. (LLM, conf=0.88)

  cites [119] Gallagher M McMahan RW Schoenbaum G Orbitofrontal cortex and representation of incentive value in associative learning J Neurosci 1999 19 6610 6614 10414988 PMC6782791 source

In the paper

“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.”

What the sources say

• Not checked yetcites [98] Volkow ND Wang GJ Telang F Inverse association between BMI and prefrontal metabolic activity in healthy adults Obesity 2009 17 60 65 18948965 PMC2681079 source

In the paper

“In this study, the metabolic activity in prefrontal regions predicted the subjects’ performance in tests of executive function (98).”

What the sources say

• Not checked yetcites [98] Volkow ND Wang GJ Telang F Inverse association between BMI and prefrontal metabolic activity in healthy adults Obesity 2009 17 60 65 18948965 PMC2681079 source

In the paper

“there is an overlap in the neuronal mechanisms implicated in the loss of control and overconsumption of food intake seen in obesity and in the compulsive intake of drugs seen in addiction.”

In the paper

“they represent a critical ‘knot’ whose fragilities are bound to underlie dysfunctional responses to a broad array of inputs, including drug and food reward.”

In the paper

“for this dimensional analysis also encompasses non-obese individuals suffering from other eating disorders (e.g. binge eating disorder [BED] and anorexia nervosa) (9,10), which are also likely to involve imbalances in reward and self-control circuits.”

What the sources say

• Not checked yetcites [9] Umberg EN Shader RI Hsu LK Greenblatt DJ From disordered eating to addiction: the ‘food drug’ in bulimia nervosa J Clin Psychopharmacol 2012 32 376 389 22544008 source
• Not checked yetcites [10] Speranza M Revah-Levy A Giquel L An investigation of Goodman’s addictive disorder criteria in eating disorders Eur Eat Disord Rev 2011 20 182 189 21834026 source

In the paper

“Drugs of abuse tap into the neuronal mechanisms that modulate the motivation to consume food”

In the paper

“Multidisciplinary research has linked such powerful craving to adaptations in the brain circuitry in charge of anticipating and assessing reward and learning conditioned associations that drive habits and automatic behaviours (7).”

What the sources say

• Not checked yetcites [7] Koob GF Le Moal M Drug abuse: hedonic homeostatic dysregulation Science 1997 278 52 58 9311926 source

In the paper

“This functional model of addiction can also be used to understand why some obese individuals find it so difficult to properly regulate their caloric intake and maintain energy homeostasis.”

In the paper

“feeding behaviours are also influenced by another layer of regulation that involves processing of rewards through DA signalling and its ability to condition food-associated stimuli that then will trigger the desire for the associated food.”

In the paper

“Several neurotransmitters, including DA, cannabinoids, opioids, gamma-aminobutyric acid (GABA) and serotonin, as well as hormones and neuropeptides involved in homeostatic regulation of food intake, such as insulin, orexin, leptin, ghrelin, PYY, glucagon-like peptide-1 (GLP-1) have been implicated in the rewarding effects of food and drugs (Tables 1 and 2) (18–21).”

What the sources say

• Not checked yetcites Tables 1 and 2
• Not checked yetcites [18] Atkinson TJ Central and peripheral neuroendocrine peptides and signalling in appetite regulation: considerations for obesity pharmacotherapy Obes Rev 2008 9 108 120 18257752 source
• Not checked yetcites [19] Cota D Tschop MH Horvath TL Levine AS Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res Rev 2006 51 85 107 16364446 source
• Not checked yetcites [20] Cason AM Smith RJ Tahsili-Fahadan P Moorman DE Sartor GC Aston-Jones G Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity Physiol Behav 2010 100 419 428 20338186 PMC2886173 source
• Not checked yetcites [21] Dickson S Shirazi RH Hansson C Bergquist F Nissbrandt H Skibicka KP The glucagon-like peptide 1 (GLP-1) analogue, Exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors J Neurosci 2012 32 4812 4820 22492036 PMC6620919 source

In the paper

“Drug addiction and obesity appear to share several properties.”

In the paper

“Central to these two pathologies is the disruption of brain dopamine (DA) pathways”

In the paper

“with repeated access to highly palatable food, some individuals (both humans as well as laboratory animals) may eventually override the inhibitory processes that signal satiety and begin to compulsively consume large amounts of food despite nutrition overload”

In the paper

“self-control and compulsive intake (whether of food or drugs) occurs in a dimensional continuum, strongly influenced by the context”

In the paper

“new genetic, pharmacological and neuroimaging evidence showing direct influences of certain peptide hormones (e.g. peptide YY [PYY], ghrelin and leptin) on DA-modulated regions including those involved in reward (VTA, NAc and ventral pallidum), self-control (prefrontal cortices), interoception (cingulate, insula), emotions (amygdala), habits and routines (dorsal striatum) and learning memory (hipp”

What the sources say

• Not checked yetcites [11] Schloegl H Percik R Horstmann A Villringer A Stumvoll M Peptide hormones regulating appetite -focus on neuroimaging studies in humans Diabetes Metab Res Rev 2011 27 104 112 21294236 source

In the paper

“The combined 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, self-control, stress reactivity and interoceptive awareness.”

In the paper

“Research is uncovering a high level of communication between these two regulatory processes, such that the line between the homeostatic and the hedonic control of feeding behaviours is becoming increasingly blurred (Tables 1 and 2).”

What the sources say

• Not checked yetcites Tables 1 and 2

In the paper

“The abrupt dopamine increases, in vulnerable individuals, can override the brain’s homeostatic control mechanisms.”

In the paper

“Most of the differences between addiction and obesity pathophysiologies arise from dysfunctions at this level of regulation, namely, energy homeostasis.”

In the paper

“Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres.”

In the paper

“drugs (and other behavioural patterns, including disordered eating) as part of a vast and heterogeneous family of ‘triggers’, with the ability to expose, under the suitable (environmental) circumstances, an underlying (biological) vulnerability.”

In the paper

“Dopamine’s role in reinforcement is more complex than just coding for hedonic pleasure.”

In the paper

“projections from the amygdala and the OFC to DA neurons and to NAc are involved in conditioned responses to food (53) and drugs (54,55).”

What the sources say

• Not checked yetcites [53] Petrovich GD Forebrain circuits and control of feeding by learned cues Neurobiol Learn Mem 2010 95 152 158 20965265 source
• Not checked yetcites [54] Lasseter HC Wells AM Xie X Fuchs RA Interaction of the basolateral amygdala and orbitofrontal cortex is critical for drug context-induced reinstatement of cocaine-seeking behavior in rats Neuropsychopharmacology 2011 36 711 720 21124303 PMC3020992 source
• Not checked yetcites [55] See RE Neural substrates of cocaine-cue associations that trigger relapse Eur J Pharmacol 2005 526 140 146 16253228 source

In the paper

“an increasing number of studies are reporting that these hormone/ peptides can modulate the rewarding effects of drugs of abuse (Table 1)”

What the sources say

• Not checked yetcites Table 1

In the paper

“Experiments in rodents have shown that, upon first exposure to a food reward, the firing of DA neurons in the VTA increases with a resulting increase in DA release in NAc (22).”

What the sources say

• Not checked yetcites [22] Norgren R Hajnal A Mungarndee SS Gustatory reward and the nucleus accumbens Physiol Behav 2006 89 531 535 16822531 PMC3114426 source

In the paper

“food-induced increases in striatal DA alone cannot explain the difference between normal food intake and excessive compulsive food consumption since these responses are present in healthy individuals who do not eat excessively.”

In the paper

“food stimuli activate brain regions that are part of the reward circuitry of the brain (45).”

What the sources say

• Not checked yetcites [45] Volkow ND Wang GJ Fowler JS Telang F Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology Philos Trans R Soc Lond B Biol Sci 2008 363 3191 3200 18640912 PMC2607335 source

In the paper

“This transition is consistent with an initial involvement of the VTA and increasing involvement of SN and its associated dorso-striatalcortical network, with consolidated responses and routines.”

In the paper

“neutral stimuli that are linked to the reinforcer (whether a natural or a drug reinforcer) acquire the ability by themselves to increase DA in striatum (including NAc) in anticipation of the reward, thus engendering a strong motivation to perform and sustain the behaviours necessary to seek the drug or to seek the food (48).”

What the sources say

• Not checked yetcites [48] Owesson-White CA Ariansen J Stuber GD Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release in the accumbens core and shell Eur J Neurosci 2009 30 1117 1127 19735286 PMC3107700 source

In the paper

“Taken together, these results strongly suggest the possibility that food and drugs may be competing for overlapping reward mechanisms.”

In the paper

“in healthy, normal-weight human subjects, ingestion of palatable food releases DA in the striatum in proportion to the ratings of meal pleasantness (44)”

What the sources say

• Not checked yetcites [44] Small DM Jones-Gotman M Dagher A Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers Neuroimage 2003 19 1709 1715 12948725 source

In the paper

“glutamatergic projections to the hypothalamus are involved in the neuroplastic changes that follow fasting and that facilitate feeding (52).”

What the sources say

• Not checked yetcites [52] Liu T Kong D Shah BP Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone Neuron 2012 73 511 522 22325203 PMC3278709 source

In the paper

“neurons in the VTA and/or NAc express GLP-1 (24,25), ghrelin (26,27), leptin (28,29), insulin (30), orexin (31) and melanocortin receptors (32).”

What the sources say

• Not checked yetcites [24] Alhadeff AL Rupprecht LE Hayes MR GLP-1 neurons in the nucleus of the solitary tract project directly to the ventral tegmental area and nucleus accumbens to control for food intake Endocrinology 2012 153 647 658 22128031 PMC3275387 source
• Not checked yetcites [25] Rinaman L Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure Brain Res 2010 1350 18 34 20353764 PMC2909454 source
• Not checked yetcites [26] Abizaid A Liu ZW Andrews ZB Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite J Clin Invest 2006 116 3229 3239 17060947 PMC1618869 source
• Not checked yetcites [27] Jerlhag E Egecioglu E Dickson SL Douhan A Svensson L Engel JA Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens Addict Biol 2007 12 6 16 17407492 source
• Not checked yetcites [28] Figlewicz D Evans SB Murphy J Hoen M Myers M Baskin DG Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat Brain Res 2003 964 107 115 12573518 source
• Not checked yetcites [29] Leshan R Opland DM Louis GW Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala J Neurosci 2010 30 5713 5723 20410123 PMC2864009 source

In the paper

“The extensive glutamatergic afferents to DA neurons from regions involved in the processing of sensory (insula or primary gustatory cortex), homeostatic (hypothalamus), reward (NAc and ventral pallidum), emotional (amygdala and hippocampus) and multimodal (orbitofrontal cortex [OFC] for salience attribution) information, modulate their activity in response to rewards and to conditioned cues (51).”

What the sources say

• Not checked yetcites [51] Geisler S Wise RA Functional implications of glutamatergic projections to the ventral tegmental area Rev Neurosci 2008 19 227 244 19145985 PMC2735573 source

In the paper

“there is also evidence of a gradual shift in DA increases from NAc to dorsal striatum, which occurs for both, food and drugs.”

In the paper

“juxtaposed interventions that decrease BMI and reduce plasma levels of insulin and leptin enhance the sensitivity to psychostimulant drugs (39).”

What the sources say

• Not checked yetcites [39] Davis JF Choi DL Benoit SC Insulin, leptin and reward Trends Endocrinol Metab 2010 21 68 74 19818643 PMC2822063 source

In the paper

“once extinguished, drug-reinforced behaviours are far more susceptible to stress-induced reinstatement than food-reinforced behaviours (58).”

What the sources say

• Not checked yetcites [58] Kearns DN Gomez-Serrano MA Tunstall BJ A review of preclinical research demonstrating that drug and non-drug rein-forcers differentially affect behavior Curr Drug Abuse Rev 2011 4 261 269 21999697 PMC3717264 source

In the paper

“Positron emission tomography (PET) studies have uncovered significant reductions in dopamine 2 receptor (D2R) availability in the striatum of addicted subjects that persist for months after protracted detoxification (reviewed in (64)).”

What the sources say

• Not checked yetcites [64] Volkow ND Fowler JS Wang GJ Baler R Telang F Imaging dopamine’s role in drug abuse and addiction Neuropharmacology 2009 56 Suppl. 1 3 8 18617195 PMC2696819 source

In the paper

“In humans addicted to drugs, the reduction in striatal D2R is associated with decreased activity of prefrontal regions, OFC, anterior cingulate gyrus (ACC) and dorsolateral prefrontal cortex (DLPFC) (67,74,75).”

What the sources say

• Not checked yetcites [67] Volkow ND Chang L Wang GJ Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex Am J Psychiatry 2001 158 2015 2021 11729018 source
• Not checked yetcites [74] Volkow ND Fowler JS Wang GJ Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers Synapse 1993 14 169 177 8101394 source
• Not checked yetcites [75] Volkow ND Wang GJ Telang F Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement J Neurosci 2007 27 12700 12706 18003850 PMC6673312 source

In the paper

“it has been postulated that their improper regulation by D2R-mediated DA signalling in addicted subjects could underlie the enhanced motivational value of drugs in their behaviour and the loss of control over drug intake (62).”

What the sources say

• Not checked yetcites [62] Volkow ND Fowler JS Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex Cereb Cortex 2000 10 318 325 10731226 source

In the paper

“A similar inhibition of the metabolic activity in the OFC (and also in NAc) has been observed in cocaine abusers when they were asked to inhibit their drug craving upon exposure to cocaine cues (57).”

What the sources say

• Not checked yetcites [57] Volkow ND Fowler JS Wang GJ Cognitive control of drug craving inhibits brain reward regions in cocaine abusers Neuroimage 2009 49 2536 2543 19913102 PMC2818484 source

In the paper

“the difference appears to be one of degree rather than principle.”

In the paper

“a study performed 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 (77).”

What the sources say

• Not checked yetcites [77] Volkow ND Wang GJ Begleiter H High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors Arch Gen Psychiatry 2006 63 999 1008 16953002 source

In the paper

“the capacity to inhibit prepotent responses and exert self-control is bound to contribute to an individual’s ability to avoid engaging in excessive behaviours, such as taking drugs or eating past the point of satiety, and thus increasing his/her vulnerability to addiction (or obesity) (62,63).”

What the sources say

• Not checked yetcites [62] Volkow ND Fowler JS Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex Cereb Cortex 2000 10 318 325 10731226 source
• Not checked yetcites [63] Volkow ND Wang GJ Telang F Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors Neuroimage 2008 42 1537 1543 18598772 PMC2659013 source

In the paper

“Evidence of dysregulated D2R striatal signalling has also been detected among obese individuals.”

In the paper

“preclinical studies in rodent and non-human primates have shown that repeated drug exposures are associated with reductions in striatal D2R levels and in D2R signalling (65–67).”

What the sources say

• Not checked yetcites [65] Thanos PK Michaelides M Benveniste H Wang GJ Volkow ND Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents Pharmacol Biochem Behav 2007 87 426 433 17599397 source
• Not checked yetcites [66] Nader MA Morgan D Gage HD PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys Nat Neurosci 2006 9 1050 1056 16829955 source
• Not checked yetcites [67] Volkow ND Chang L Wang GJ Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex Am J Psychiatry 2001 158 2015 2021 11729018 source

In the paper

“when compared to food cues, drug cues are more powerful triggers of reinforcer-seeking behaviour following a period of abstinence, at least in the case of animals that have not been food deprived (58).”

What the sources say

• Not checked yetcites [58] Kearns DN Gomez-Serrano MA Tunstall BJ A review of preclinical research demonstrating that drug and non-drug rein-forcers differentially affect behavior Curr Drug Abuse Rev 2011 4 261 269 21999697 PMC3717264 source

In the paper

“This blunted response to food consumption in the reward circuitry of obese individuals is reminiscent of the reduced DA increases triggered by drug consumption in addicted individuals when compared to non-addicted subjects (94).”

What the sources say

• Not checked yetcites [94] Volkow ND Wang GJ Fowler JS Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects Nature 1997 386 830 833 9126741 source

In the paper

“However, studies performed with obese individuals have begun to uncover evidence of a preference for high, immediate rewards, despite an increased chance of suffering higher future losses (100,101).”

What the sources say

• Not checked yetcites [100] Brogan A Hevey D Pignatti R Anorexia, bulimia, and obesity: shared decision making deficits on the Iowa Gambling Task (IGT) J Int Neuropsychol Soc 2010 16 711 715 20406532 source
• Not checked yetcites [101] Weller RE Cook EW3rd Avsar KB Cox JE Obese women show greater delay discounting than healthy-weight women Appetite 2008 51 563 569 18513828 source

In the paper

“Dopaminergic signalling also modulates motivation.”

What the sources say

• Not checked yetcites [108] Salamone JD Correa M Farrar A Mingote SM Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits Psychopharmacology (Berl) 2007 191 461 482 17225164 source

In the paper

“Interestingly, delay discounting seems to depend on the function of the ventral striatum (104) and of the PFC, including OFC (105) and its connections to the NAc (106), and is sensitive to DA manipulations (107).”

What the sources say

• Not checked yetcites [104] Gregorios-Pippas L Tobler PN Schultz W Short-term temporal discounting of reward value in human ventral striatum J Neurophysiol 2009 101 1507 1523 19164109 PMC2666398 source

In the paper

“the one study that failed to detect a statistically significant reduction in striatal D2R between obese individuals and non-obese controls (83), may have been hampered by its low statistical power (n = 5/group).”

What the sources say

• Not checked yetcites [83] Steele KE Prokopowicz GP Schweitzer MA Alterations of central dopamine receptors before and after gastric bypass surgery Obes Surg 2010 20 369 374 19902317 source

In the paper

“Interestingly, delay discounting seems to depend on the function of the ventral striatum (104) and of the PFC, including OFC (105) and its connections to the NAc (106), and is sensitive to DA manipulations (107).”

What the sources say

• Not checked yetcites [105] Bjork JM Momenan R Hommer DW Delay discounting correlates with proportional lateral frontal cortex volumes Biol Psychiatry 2009 65 710 713 19121516 source

In the paper

“compared with normal-weight individuals, obese individuals who were presented with pictures of high-calorie food (stimuli to which they are conditioned) showed increased neural activation in regions that are part of reward and motivation circuits (NAc, dorsal striatum, OFC, ACC, amygdala, hippocampus and insula) (90).”

What the sources say

• Not checked yetcites [90] Killgore WD Yurgelun-Todd DA Body mass predicts orbitofrontal activity during visual presentations of high-calorie foods Neuroreport 2005 16 859 863 15891585 source

In the paper

“Behavioural traits such as vigor, persistence and investing a continued effort towards 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 (108).”

What the sources say

• Not checked yetcites [108] Salamone JD Correa M Farrar A Mingote SM Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits Psychopharmacology (Berl) 2007 191 461 482 17225164 source

In the paper

“The hypothesis of compensatory overeating is consistent with preclinical evidence showing that decreased DA activity in VTA results in a dramatic increase in the consumption of high-fat foods (89).”

What the sources say

• Not checked yetcites [89] Stoeckel LE Weller RE Cook EW3rd Twieg DB Knowlton RC Cox JE Widespread reward-system activation in obese women in response to pictures of high-calorie foods Neuroimage 2008 41 636 647 18413289 source

In the paper

“Delay discounting has been most exhaustively investigated in drug abusers who exhibit an exaggerated preference of small-but-immediate over large-but-delayed rewards (99).”

What the sources say

• Not checked yetcites [99] Bickel WK Miller ML Yi R Kowal BP Lindquist DM Pitcock JA Behavioral and neuroeconomics of drug addiction: competing neural systems and temporal discounting processes Drug Alcohol Depend 2007 90 Suppl. 1 S85 S91 17101239 PMC2033431 source

In the paper

“Interestingly, delay discounting seems to depend on the function of the ventral striatum (104) and of the PFC, including OFC (105) and its connections to the NAc (106), and is sensitive to DA manipulations (107).”

What the sources say

• Not checked yetcites [106] Bezzina G Body S Cheung TH Effect of disconnecting the orbital prefrontal cortex from the nucleus accumbens core on inter-temporal choice behaviour: a quantitative analysis Behav Brain Res 2008 191 272 279 18472170 PMC2424131 source

In the paper

“in normal-weight controls, the activation of the ACC and OFC (regions involved in salience attribution that project into the NAc) during presentation of high-calorie food was found to be negatively correlated with their BMI (91).”

What the sources say

• Not checked yetcites [91] Stice E Spoor S Bohon C Veldhuizen MG Small DM Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study J Abnorm Psychol 2008 117 924 935 19025237 PMC2681092 source

In the paper

“A recent functional magnetic resonance imaging (fMRI) study of executive function in obese women, for example, identified regional differences in brain activation during delayed discounting tasks that were predictive of future weight gain (102).”

What the sources say

• Not checked yetcites [102] Kishinevsky FI Cox JE Murdaugh DL Stoeckel LE Cook EW3rd Weller RE fMRI reactivity on a delay discounting task predicts weight gain in obese women Appetite 2012 58 582 592 22166676 source

In the paper

“it is also possible that some eating disorders may actually result from hypersensitivity to conditioned food cues.”

In the paper

“Yet, another study found a positive correlation between BMI and hyperbolic discounting, whereby future negative payoffs are discounted less than future positive payoffs (103).”

What the sources say

• Not checked yetcites [103] Ikeda S Kang MI Ohtake F Hyperbolic discounting, the sign effect, and the body mass index J Health Econ 2010 29 268 284 20167384 source

In the paper

“Interestingly, delay discounting seems to depend on the function of the ventral striatum (104) and of the PFC, including OFC (105) and its connections to the NAc (106), and is sensitive to DA manipulations (107).”

What the sources say

• Not checked yetcites [107] Pine A Shiner T Seymour B Dolan RJ Dopamine, time, and impulsivity in humans J Neurosci 2010 30 8888 8896 20592211 PMC3059485 source

In the paper

“In addition, a study that prompted cocaine-addicted subjects to purposefully inhibit craving when exposed to drug cues showed that those subjects who were successful at inhibiting craving displayed decreased metabolism in medial OFC (which processes the motivational value of a reinforcer) and NAc (which predicts reward) (57).”

What the sources say

• Not checked yetcites [57] Volkow ND Fowler JS Wang GJ Cognitive control of drug craving inhibits brain reward regions in cocaine abusers Neuroimage 2009 49 2536 2543 19913102 PMC2818484 source

In the paper

“Another study found no differences in grey 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 (129).”

What the sources say

• Not checked yetcites [129] Haltia LT Viljanen A Parkkola R Brain white matter expansion in human obesity and the recovering effect of dieting J Clin Endocrinol Metab 2007 92 3278 3284 17536002 source

In the paper

“Dysregulated DA signalling is associated with enhanced motivation to procure drugs, a hallmark of addiction, which is why drug-addicted individuals often engage in extreme behaviours to obtain drugs, even when they entail known severe and adverse consequences and may require sustained and complex behaviours to obtain them (109).”

What the sources say

• Not checked yetcites [109] Volkow N Li TK The neuroscience of addiction Nat Neurosci 2005 8 1429 1430 16251981 source

In the paper

“Interestingly, albeit predictably, a cross-sectional investigation of children’s ability to self-regulate, solve problems and engage in goal-directed health behaviours reveals executive function proficiency to be negatively correlated not only with substance use but also with the consumption of high-calorie snack foods, and with sedentary behaviours (125).”

What the sources say

• Not checked yetcites [125] Riggs NR Spruijt-Metz D Chou CP Pentz MA Relationships between executive cognitive function and lifetime substance use and obesity-related behaviors in fourth grade youth Child Neuropsychol 2012 18 1 11 21480013 source

In the paper

“Because drug taking becomes the main motivational drive in drug addiction (110), 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.”

What the sources say

• Not checked yetcites [110] Volkow ND Fowler JS Wang GJ The addicted human brain: insights from imaging studies J Clin Invest 2003 111 1444 1451 12750391 PMC155054 source

In the paper

“These findings further corroborate the involvement of OFC, ACC and striatum in the enhanced motivation to procure the drug seen in addiction.”

In the paper

“The OFC plays a role in learning stimulus-reinforcement associations and conditioning (118,119), supports conditioned-cue-elicited feeding (120) and probably contributes to overeating irrespective of hunger signals (121).”

What the sources say

• Not checked yetcites [121] Ogden J Wardle J Cognitive restraint and sensitivity to cues for hunger and satiety Physiol Behav 1990 47 477 481 2359756 source

In the paper

“In contrast to the decreases in prefrontal activity reported in detoxified cocaine abusers when not stimulated with drug or drug cues (see review (64)), these prefrontal regions become activated when cocaine abusers are exposed to craving-inducing stimuli (either drugs or cues) (111–113).”

What the sources say

• Not checked yetcites [64] Volkow ND Fowler JS Wang GJ Baler R Telang F Imaging dopamine’s role in drug abuse and addiction Neuropharmacology 2009 56 Suppl. 1 3 8 18617195 PMC2696819 source

In the paper

“In contrast to the decreases in prefrontal activity reported in detoxified cocaine abusers when not stimulated with drug or drug cues (see review (64)), these prefrontal regions become activated when cocaine abusers are exposed to craving-inducing stimuli (either drugs or cues) (111–113).”

What the sources say

• Not checked yetcites [111] Volkow ND Wang GJ Fowler JS Association of methylphenidate-induced craving with changes in right striatoorbitofrontal metabolism in cocaine abusers: implications in addiction Am J Psychiatry 1999 156 19 26 9892293 source
• Not checked yetcites [112] Wang GJ Volkow ND Fowler JS Regional brain metabolic activation during craving elicited by recall of previous drug experiences Life Sci 1999 64 775 784 10075110 source
• Not checked yetcites [113] Grant S London ED Newlin DB Activation of memory circuits during cue-elicited cocaine craving Proc Natl Acad Sci U S A 1996 93 12040 12045 8876259 PMC38179 source

In the paper

“Another study found no differences in grey 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 (129).”

What the sources say

• Not checked yetcites [129] Haltia LT Viljanen A Parkkola R Brain white matter expansion in human obesity and the recovering effect of dieting J Clin Endocrinol Metab 2007 92 3278 3284 17536002 source

In the paper

“The OFC is also involved in attributing salience value to food (115,116), helping to assess its expected pleasantness and palatability as a function of its context.”

What the sources say

• Not checked yetcites [115] Rolls ET McCabe C Enhanced affective brain representations of chocolate in cravers vs. non-cravers Eur J Neurosci 2007 26 1067 1076 17714197 source
• Not checked yetcites [116] Grabenhorst F Rolls ET Bilderbeck A How cognition modulates affective responses to taste and flavor: top-down influences on the orbitofrontal and pregenual cingulate cortices Cereb Cortex 2008 18 1549 1559 18056086 source

In the paper

“Brain imaging studies comparing obese and lean individuals have also reported lower grey matter density in frontal regions (frontal operculum and middle frontal gyrus) and in post-central gyrus and putamen (128).”

What the sources say

• Not checked yetcites [128] Pannacciulli N Del Parigi A Chen K Le DS Reiman EM Tataranni PA Brain abnormalities in human obesity: a voxel-based morphometric study Neuroimage 2006 31 1419 1425 16545583 source

In the paper

“Clearly, some of the individual differences in executive function can constitute a prodromal risk for later obesity in some individuals, as revealed by a recent latent class analysis of 997 fourth graders in a school-based obesity prevention program (124).”

What the sources say

• Not checked yetcites [124] Riggs NR Huh J Chou CP Spruijt-Metz D Pentz MA Executive function and latent classes of childhood obesity risk J Behav Med 2012 in press 22218938 source

In the paper

“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 (130), suggesting a potential target for behavioural retraining in the treatment of obesity (and also in addiction).”

What the sources say

• Not checked yetcites [130] DelParigi A Chen K Salbe AD Successful dieters have increased neural activity in cortical areas involved in the control of behavior Int J Obes (Lond) 2007 31 440 448 16819526 source

In the paper

“In spite of some inconsistencies among studies, brain imaging data also support the notion that structural and functional changes in brain regions implicated in executive function (including inhibitory control) may be associated with high BMI in otherwise healthy individuals.”

In the paper

“Neuroimaging studies have revealed that the middle insula plays a critical role in cravings for food, cocaine and cigarettes (131–133).”

What the sources say

• Not checked yetcites [131] Bonson KR Grant SJ Contoreggi CS Neural systems and cue-induced cocaine craving Neuropsychopharmacology 2002 26 376 386 11850152 source
• Not checked yetcites [132] Pelchat ML Johnson A Chan R Valdez J Ragland JD Images of desire: food-craving activation during fMRI Neuroimage 2004 23 1486 1493 15589112 source
• Not checked yetcites [133] Wang Z Faith M Patterson F Neural substrates of abstinence-induced cigarette cravings in chronic smokers J Neurosci 2007 27 14035 14040 18094242 PMC2153440 source

In the paper

“The OFC plays a role in learning stimulus-reinforcement associations and conditioning (118,119), supports conditioned-cue-elicited feeding (120) and probably contributes to overeating irrespective of hunger signals (121).”

What the sources say

• Not checked yetcites [120] Weingarten HP Conditioned cues elicit feeding in sated rats: a role for learning in meal initiation Science 1983 220 431 433 6836286 source

In the paper

“Similarly, a nuclear magnetic resonance spectroscopic study in healthy middle age and elderly controls showed that BMI was negatively associated with the levels of N-acetyl-aspartate (a marker of neuronal integrity) in frontal cortex and ACC (98,127).”

What the sources say

• Not checked yetcites [98] Volkow ND Wang GJ Telang F Inverse association between BMI and prefrontal metabolic activity in healthy adults Obesity 2009 17 60 65 18948965 PMC2681079 source
• Not checked yetcites [127] Gazdzinski S Kornak J Weiner MW Meyerhoff DJ Body mass index and magnetic resonance markers of brain integrity in adults Ann Neurol 2008 63 652 657 18409192 PMC2542059 source

In the paper

“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 (130), suggesting a potential target for behavioural retraining in the treatment of obesity (and also in addiction).”

In the paper

“Dysregulated DA signalling is associated with enhanced motivation to procure drugs, a hallmark of addiction, which is why drug-addicted individuals often engage in extreme behaviours to obtain drugs, even when they entail known severe and adverse consequences and may require sustained and complex behaviours to obtain them (109).”

What the sources say

• Not checked yetcites [109] Volkow N Li TK The neuroscience of addiction Nat Neurosci 2005 8 1429 1430 16251981 source

In the paper

“Indeed, damage to the OFC can result in hyperphagia (122,123).”

What the sources say

• Not checked yetcites [122] Machado CJ Bachevalier J The effects of selective amygdala, orbital frontal cortex or hippocampal formation lesions on reward assessment in nonhuman primates Eur J Neurosci 2007 25 2885 2904 17561849 source
• Not checked yetcites [123] Maayan L Hoogendoorn C Sweat V Convit A Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction Obesity (Silver Spring) 2011 19 1382 1387 21350433 PMC3124611 source

In the paper

“In the case of nicotine, a5 nicotinic receptors in the habenula appear to modulate the aversive responses to large doses of nicotine (155), and a5 and a2 receptors to modulate nicotine withdrawal (156).”

What the sources say

• Not checked yetcites [155] Fowler CD Lu Q Johnson PM Marks MJ Kenny PJ Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake Nature 2011 471 597 601 21278726 PMC3079537 source

In the paper

“Thus, an enhanced sensitivity of the habenula, as a result of chronic drug exposures, could underlie a greater reactivity to drug cues when not followed by consumption of the drug or when the drug effects do not fulfil the expected reward outcome.”

In the paper

“The habenula appears to play a similar role with regards to food reward.”

In the paper

“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 trigger the desire to ingest the food/ drug.”

In the paper

“And indeed, gastric distension results in activation of the posterior insula, consistent with its role in the awareness of body states (in this case of fullness) (140).”

What the sources say

• Not checked yetcites [140] Wang GJ Tomasi D Backus W Gastric distention activates satiety circuitry in the human brain Neuroimage 2008 39 1824 1831 18155924 source

In the paper

“In the case of nicotine, a5 nicotinic receptors in the habenula appear to modulate the aversive responses to large doses of nicotine (155), and a5 and a2 receptors to modulate nicotine withdrawal (156).”

What the sources say

• Not checked yetcites [156] Salas R Sturm R Boulter J De Biasi M Nicotinic receptors in the habenulointerpeduncular system are necessary for nicotine withdrawal in mice J Neurosci 2009 29 3014 3018 19279237 PMC3862238 source

In the paper

“Cumulative evidence (148–151) points to the habenula as one of the regions that controls the decreases in firing of dopaminergic cells in VTA that may follow the failure to receive an expected reward (152).”

What the sources say

• Not checked yetcites [148] Matsumoto M Hikosaka O Lateral habenula as a source of negative reward signals in dopamine neurons Nature 2007 447 1111 1115 17522629 source
• Not checked yetcites [149] Christoph GR Leonzio RJ Wilcox KS Stimulation of the lateral habenula inhibits dopamine-containing neurons in the sub-stantia nigra and ventral tegmental area of the rat J Neurosci 1986 6 613 619 3958786 PMC6568453 source
• Not checked yetcites [150] Lisoprawski A Herve D Blanc G Glowinski J Tassin JP Selective activation of the mesocortico-frontal dopaminergic neurons induced by lesion of the habenula in the rat Brain Res 1980 183 229 234 7357405 source

In the paper

“This suggests that the habenula may be involved in over-eating when palatable food is available.”

In the paper

“Obese subjects exhibit greater insular activation than normal controls when tasting a liquid meal that consists of sugar and fat (143).”

What the sources say

• Not checked yetcites [143] DelParigi A Chen K Salbe AD Reiman EM Tataranni PA Sensory experience of food and obesity: a positron emission tomography study of the brain regions affected by tasting a liquid meal after a prolonged fast Neuroimage 2005 24 436 443 15627585 source

In the paper

“The importance of the insula has been highlighted by a study that reported that smokers with damage to this region (but not smokers who had suffered extra-insular lesions) were able to stop smoking easily and without experiencing either cravings or relapse (134).”

What the sources say

• Not checked yetcites [134] Naqvi NH Rudrauf D Damasio H Bechara A Damage to the insula disrupts addiction to cigarette smoking Science 2007 315 531 534 17255515 PMC3698854 source

In the paper

“Indeed, activation of the habenula, in animal models of cocaine addiction, has been associated with relapse to drug taking upon cue exposure (153,154).”

What the sources say

• Not checked yetcites [153] Zhang F Zhou W Liu H Increased c-Fos expression in the medial part of the lateral habenula during cue-evoked heroin-seeking in rats Neurosci Lett 2005 386 133 137 16002220 source
• Not checked yetcites [154] Brown RM Short JL Lawrence AJ Identification of brain nuclei implicated in cocaine-primed reinstatement of conditioned place preference: a behaviour dissociable from sensitization Plos ONE 2011 5 e15889 21209913 PMC3012115 source

In the paper

“Consistent with this hypothesis, many imaging studies show differential activation of the insula during craving (135).”

What the sources say

• Not checked yetcites [135] Naqvi NH Bechara A The hidden island of addiction: the insula Trends Neurosci 2009 32 56 67 18986715 PMC3698860 source

In the paper

“Because of the insula’s involvement in the interoceptive sense of the body, in emotional awareness (139) and in motivation and emotion (138), a contribution of insular impairment in obesity should not be surprising.”

In the paper

“In addition, the rostral insula (connected to primary taste cortex) provides information to the OFC that influences its multimodal representation of the pleasantness or reward value of incoming food (138).”

What the sources say

• Not checked yetcites [138] Rolls ET Functions of the orbitofrontal and pregenual cingulate cortex in taste, olfaction, appetite and emotion Acta Physiol Hung 2008 95 131 164 18642756 source

In the paper

“Indeed, brain lesion studies suggest that the ventromedial PFC and insula are necessary components of the distributed circuits that support emotional decision-making (136).”

What the sources say

• Not checked yetcites [136] Clark L Bechara A Damasio H Aitken MR Sahakian BJ Robbins TW Differential effects of insular and ventromedial pre-frontal cortex lesions on risky decision-making Brain 2008 131 1311 1322 18390562 PMC2367692 source

In the paper

“The lack of amygdalar response in obese subjects could reflect a blunted interoceptive awareness of bodily states linked with satiety (full stomach).”

In the paper

“These findings are consistent with a role for the habenula (both medial and lateral) in mediating responses to aversive stimuli or to states of deprivation such as during dieting or drug withdrawal.”

In the paper

“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 (135).”

What the sources say

• Not checked yetcites [135] Naqvi NH Bechara A The hidden island of addiction: the insula Trends Neurosci 2009 32 56 67 18986715 PMC3698860 source

In the paper

“On the other hand, and consistent with this logic, it has been observed that dopaminergic cells will fire less than normal if the expected reward fails to materialize (147).”

What the sources say

• Not checked yetcites [147] Schultz W Dayan P Montague PR A neural substrate of prediction and reward Science 1997 275 1593 1599 9054347 source

In the paper

“DA signalling may also be necessary for sensing the calorie content of food.”

In the paper

“The involvement of the habenula as an antireward hub within emotional networks is consistent with prior theoretical models of addiction that postulated that sensitized stress reactivity and negative mood (mediated through enhanced sensitivity of the amygdala and increased signalling although the corticotrophin-releasing factor) drives drug intake in addiction (159).”

What the sources say

• Not checked yetcites [159] Koob GF Le Moal M Addiction and the brain antireward system Annu Rev Psychol 2008 59 29 53 18154498 source

In the paper

“Furthermore, a recent fMRI study that compared brain responses to repeated presentations of appetizing and bland food pictures in morbidly obese vs. non-obese individuals (146) found functional changes in the responsiveness and interconnectivity among key regions of the reward circuit that might help explain the oversensitivity to food cues in obese individuals.”

What the sources say

• Not checked yetcites [146] Nummenmaa L Hirvonen J Hannukainen JC Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity Plos ONE 2012 7 e31089 22319604 PMC3272045 source

In the paper

“Interestingly, the medial habenula showed significantly higher m-opioid peptide binding (by approximately 40%) after exposure to the palatable food in the rats that gained weight (those that consumed more food) but not in those that did not (157).”

What the sources say

• Not checked yetcites [157] Smith SL Harrold JA Williams G Diet-induced obesity increases mu opioid receptor binding in specific regions of the rat brain Brain Res 2002 953 215 222 12384255 source