Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans

Zald, David H.; Cowan, Ronald L.; Riccardi, Patrizia; Baldwin, Ronald M.; Ansari, M. Sib; Li, Rui; Shelby, Evan; Smith, Clarence E.; McHugo, Maureen; Kessler, Robert

doi:10.1523/jneurosci.2423-08.2008

Cited by 215 publications

(173 citation statements)

References 74 publications

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“…Increased novelty seeking has been associated with increased risk for substance abuse and dependence 53,54 and with reduced midbrain dopamine receptor availability. 55 It is possible that novelty seeking may not be a strong risk factor for obesity because, unlike drugs of abuse, humans are exposed to food on a daily basis. According to the incentive-sensitization model of addiction, neural modification of the dopaminergic mesolimbic system by exposure to addictive drugs leads to hypersensitization of the reward system to drug-related stimuli.…”

Section: Discussionmentioning

confidence: 99%

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

et al. 2009

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Background:The major aim of this study was to investigate whether the motivational salience of food cues (as reflected by their attention-grabbing properties) differs between obese and normal-weight subjects in a manner consistent with altered reward system function in obesity. Methodology/Principal Findings: A total of 18 obese and 18 normal-weight, otherwise healthy, adult women between the ages of 18 and 35 participated in an eye-tracking paradigm in combination with a visual probe task. Eye movements and reaction time to food and non-food images were recorded during both fasted and fed conditions in a counterbalanced design. Eating behavior and hunger level were assessed by self-report measures. Obese individuals had higher scores than normalweight individuals on self-report measures of responsiveness to external food cues and vulnerability to disruptions in control of eating behavior. Both obese and normal-weight individuals demonstrated increased gaze duration for food compared to nonfood images in the fasted condition. In the fed condition, however, despite reduced hunger in both groups, obese individuals maintained the increased attention to food images, whereas normal-weight individuals had similar gaze duration for food and non-food images. Additionally, obese individuals had preferential orienting toward food images at the onset of each image. Obese and normal-weight individuals did not differ in reaction time measures in the fasted or fed condition. Conclusions/Significance: Food cue incentive salience is elevated equally in normal-weight and obese individuals during fasting. Obese individuals retain incentive salience for food cues despite feeding and decreased self-report of hunger. Sensitization to food cues in the environment and their dysregulation in obese individuals may play a role in the development and/or maintenance of obesity.

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Section: Discussionmentioning

confidence: 99%

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

et al. 2009

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“…Excessive NS has been consistently linked to several neuropsychiatric disorders, including substance abuse (4), pathologic gambling (34), and eating disorders (35). Although the role of dopamine in driving NS behaviors has been largely confirmed (36)(37)(38), the involvement of other neurotransmitter systems remains scarcely studied. Positive correlation between mGluR5 availability ( 18 F-FPEB V T ) in limbic areas and temperament trait NS.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we did not observe associations between mGluR5 and NS in core regions of the reward circuitry, that is, the ventral tegmental area and the ventral striatum. Though this aspect of NS might primarily be related to dopamine signaling in humans (36), a recent study found that specific inactivation of mGluR5 signaling in D1-dopaminoceptive neurons abolishes NS behaviors in rodents (16), still suggesting that some dopaminergic-glutamatergic interactions are involved in NS behaviors. Lastly, the insula is a paralimbic region critically involved in determining the emotionalmotivational salience of various somatosensory stimuli (41), a key aspect of NS.…”

Section: Discussionmentioning

confidence: 99%

Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An ¹⁸F-FPEB PET Study

et al. 2016

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Heritable temperament traits have been linked to several neuropsychiatric illnesses, including disorders associated with metabotropic glutamate receptor 5 (mGluR5) and dopaminergic dysfunctions. Considering its modulating effect on neurotransmission, we hypothesized that cerebral mGluR5 availability is associated with temperament traits in healthy humans. Methods: Forty-four nonsmoking healthy volunteers (mean age ± SD, 40 ± 14 y; age range, 22-66 y; 22 women) were included in this cross-sectional investigation. Brain mGluR5 availability was quantified on both a voxel-by-voxel and a volume-of-interest basis using the total distribution volume of the radioligand 18 F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ( 18 F-FPEB) with 90-min dynamic PET and arterial input function. Moreover, glutamate-glutamine concentrations in the anterior cingulate cortex were measured using MR spectroscopy. These measures were related to the temperament traits of the 240-item Cloninger temperament and character inventory using a regression analysis with age and sex as nuisance variables. Results: High novelty-seeking temperament was robustly associated with increased mGluR5 availability in various regions including the thalamus (r 5 0.71; the strongest association), amygdala, parahippocampus, insula, anterior and posterior cingulate cortex, and several primary sensory areas (all r . 0.58; P , 0.05, corrected for familywise error). These associations were specific because no correlations were found with other temperament scales or with spectroscopic measures of glutamatergic transmission. Conclusion: Overall, these data posit mGluR5 in key paralimbic areas as a strong determinant of the temperament trait novelty seeking. These data add to our understanding of how brain neurochemistry accounts for the variation in human behavior and strongly support further research on mGluR5 as a potential therapeutic target in neuropsychiatric disorders associated with abnormal novelty-seeking behaviors. Theneur obiologic substrates of human personality and behavior remain an important but complex area of neuroscience. More than 20 y ago, the Cloninger's theory of personality represented one of the first attempts to integrate neurotransmitter systems into personality research (1). This model identified 7 personality traits, that is, 4 temperaments and 3 characters. Temperaments are thought to be independently inherited with specific brain circuits and stable over a lifetime, whereas character dimensions are suggested to form over time through the interplay of genetic and environmental factors. Subsequently, genetic determinants of receptor expression and neuronal function in the normal variation of human behavior have been validated (2). Several temperament and personality traits, including novelty seeking (NS), harm avoidance, and impulsivity, have been associated with the vulnerability to mental illnesses (3,4) and have been directly related to receptors and neurotransmission using functional imaging (5-7). In parallel, dysregulation or disequi...

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“…Recent studies report correlations between NS scores and interindividual differences in human dopaminergic brain regions in terms of functional activation (Abler et al, 2006;Naghavi et al, 2009), dopamine ligand binding (Zald et al, 2008) and connectivity with other brain regions (Cohen et al, 2009). To ensure that the genotypedependent differences in activation we describe are independent of NS, we repeated our statistical analyses including NS as an additional covariate.…”

Section: Imaging Responses To Perceptual Oddballsmentioning

confidence: 99%

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

et al. 2014

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Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the -5210T DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic-hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region.

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Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans

Cited by 215 publications

References 74 publications

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An ¹⁸F-FPEB PET Study

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

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Midbrain Dopamine Receptor Availability Is Inversely Associated with Novelty-Seeking Traits in Humans

Cited by 215 publications

References 74 publications

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

Obese adults have visual attention bias for food cue images: evidence for altered reward system function

Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An 18F-FPEB PET Study

Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

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Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An ¹⁸F-FPEB PET Study