Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking

Gjedde, Albert; Kumakura, Yoshitaka; Cumming, Paul; Linnet, Jakob; Møller, Arne

doi:10.1073/pnas.0912319107

Cited by 125 publications

(124 citation statements)

References 37 publications

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“…Animal studies have demonstrated that testosterone significantly influences dopamine neural transmission in the adolescent brain (Allen et al, 2015). Furthermore, dopamine receptor density has been shown to correlate with motivational forms of impulsive behaviour (sensation seeking) in adult men (Gjedde et al, 2010). In addition, Braams and colleagues (2015) have shown that pubertal testosterone is associated with an increased response to rewards in the striatum.…”

Section: Introductionmentioning

confidence: 98%

Dissociable effects of age and testosterone on adolescent impatience

Laube

Suleiman

Johnson

et al. 2017

Psychoneuroendocrinology

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a b s t r a c tThe onset of adolescence is associated with an increase in transgressive behaviours-from juvenile delinquency to substance use and unprotected sex-that are often attributed to increased impulsiveness. In the past, this increase was ascribed to "raging hormones"; more recently, to an imbalance in the maturation of different brain regions. However, it remains unclear how these large-scale biological changes impact specific processes that result in impulsive decisions, namely, sensitivity to immediate rewards and general discounting of future options. To gain further insight into these questions, we used an intertemporal choice task to investigate the role of testosterone in impatient decision-making in boys at the developmental transition to adolescence (N = 72, ages 11-14). Our results suggest that increased testosterone (but not age) is related to increased sensitivity to immediate rewards, whereas increased age (but not testosterone) is related to a reduction in general impatience. These results are discussed in the context of recent neurobiological models of adolescent development.

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Section: Introductionmentioning

confidence: 98%

Dissociable effects of age and testosterone on adolescent impatience

Laube

Suleiman

Johnson

et al. 2017

Psychoneuroendocrinology

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“…In this study, the authors suggest that the given dose may have been too high for those with higher DA D 2 levels, and that a smaller dose may have had a more pleasant effect, suggesting that drug abusers in general suffer from lower DA gains in the striatum (17,19,25).…”

Section: Addiction and Dopaminementioning

confidence: 93%

“…Drug abusers in general have low DA D 2 receptor levels in striatum and a low DA release (17), which is linked to the observation that repeated intake of addictive substances such as amphetamine or cocaine significantly downregulates available DA D 2 receptor levels, understandable as a compensation for the high and persistent DA concentration in the synaptic cleft (18). Gjedde et al (19) showed that healthy Danish men who are more sensation-seeking than other healthy men have significantly fewer available DA receptors in striatum because a greater fraction are occupied by the increased extracellular DA. This greater dopamine in turn is thought to be the result of constant dopaminergic stimulation, yielding the lower binding potential (BP) of the receptors.…”

Section: Addiction and Dopaminementioning

confidence: 99%

Perspective food addiction, caloric restriction, and dopaminergic neurotransmission

Stankowska

Gjedde

2013

Acta Neuropsychiatr.

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Stankowska AUM, Gjedde A. Perspective food addiction, caloric restriction, and dopaminergic neurotransmission.People attempt to change their lifestyle when obesity impairs their quality of life. The attempts often fail when multiple habits must be changed in unison. Here we explore relations among food addiction, the neurobiology of habits, and caloric restriction, when people seek to return to normal eating behaviour, with particular emphasis on the role of dopaminergic neurotransmission. Severely obese individuals have specific neurobiological characteristics in common with drug abusers, including low availability of dopamine receptors in the striatum, impaired neuronal responses to dopamine, and reduced activity in prefrontal regions of the cerebral cortex. The neurobiological characteristics suggest that obese people also have a pathological dependence in common with addicts, in the form of food addiction. Malnutrition and dieting both relate to binge eating, possibly as a compensation for a reduced cognitive reward condition. The combination of caloric restriction and food addiction imparts a high risk of relapse as a result of further reduction of dopaminergic neurotransmission and the subsequent loss of reward. As with drugs of abuse, ingestion of large quantities of sugar in circumstances of uncontrolled eating increases dopamine release in the nucleus accumbens. This and other evidence suggests that abuse of food is a habit learned by means of mechanisms centred in the basal ganglia, with an increased risk of relapse in the presence of associative amplifiers. This risk is predicted by the relationship between dopamine receptor availability in the striatum and sensation-seeking in the form of an inverted U, suggested by recent findings, consistent with two opposite states of hypodopaminergic and hyperdopaminergic neuromodulation. Summations> With neurobiological similarities among the brain functions of individuals with behaviour suggestive of addiction, obese individuals with reduced reward sensitivity suffer from pathological addiction to food. > Both undernutrition and dieting are positively correlated with strong craving for food and accompanying overeating, evidently as a compensation for reduced activity of neurobiological reward mechanisms. > The combination of caloric restriction and food addiction alone has a high risk of continued bouts of overeating as results of the reduced gain from dopaminergic neurotransmission maintained by repeated relapses. The risk can be diminished by lifestyle modifications that at the very least include exercise and counselling or group therapy. The inverted U-shaped model is a measure of the efficiency of a given individual's reward system. Considerations> The neurobiological similarities among the brain functions of individuals with behaviour suggestive of addiction suggest but do not prove that obese individuals with reduced reward sensitivity in fact suffer from an addiction.

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“…We calculated BP ND as the ratio of the volume V T in ROIs with specifically displaceable binding and the volume V ND of distribution in a chosen reference region with specifically nondisplaceable binding, here selected as the volume determined for the corpus callosum (BP ND 5 0) (22).…”

Section: Kinetic Analysis Of 11 C-yohimbine Uptake and Distributionmentioning

confidence: 99%

Mapping α₂ Adrenoceptors of the Human Brain with ¹¹C-Yohimbine

et al. 2015

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A previous study from this laboratory suggested that 11 C-yohimbine, a selective α 2 -adrenoceptor antagonist, is an appropriate ligand for PET of α 2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood-brain clearances, volumes of distribution, and receptor availability by means of PET with 11 C-yohimbine in healthy male adults. Methods: We recorded the distribution of 11 C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact 11 C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of 11 C-yohimbine. With the lowest steady-state distribution volume (V T ), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions. Results: The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of V T ranged from 0.82 mL cm −3 in the right frontal cortex to 0.46 mL cm −3 in the corpus callosum, with intermediate V T values in subcortical structures. Binding potentials averaged 0.6-0.8 in the cortex and 0.2-0.5 in subcortical regions. Conclusion: The maps of 11 Cyohimbine binding to α 2 adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11 C-yohimbine for mapping α 2 adrenoceptors in human brain in vivo.

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Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking

Cited by 125 publications

References 37 publications

Dissociable effects of age and testosterone on adolescent impatience

Dissociable effects of age and testosterone on adolescent impatience

Perspective food addiction, caloric restriction, and dopaminergic neurotransmission

Mapping α₂ Adrenoceptors of the Human Brain with ¹¹C-Yohimbine

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Inverted-U-shaped correlation between dopamine receptor availability in striatum and sensation seeking

Cited by 125 publications

References 37 publications

Dissociable effects of age and testosterone on adolescent impatience

Dissociable effects of age and testosterone on adolescent impatience

Perspective food addiction, caloric restriction, and dopaminergic neurotransmission

Mapping α2 Adrenoceptors of the Human Brain with 11C-Yohimbine

Contact Info

Product

Resources

About

Mapping α₂ Adrenoceptors of the Human Brain with ¹¹C-Yohimbine