In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO

Boileau, Isabelle; Payer, Doris; Chugani, Bindiya; Lobo, Daniela S. S.; Houle, Sylvain; Wilson, Alan A.; Warsh, Jerry J.; Kish, Stephen J.; Zack, Martin

doi:10.1038/mp.2013.163

Cited by 180 publications

(137 citation statements)

References 75 publications

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“…For instance, in contrast to studies in cocaine and alcohol addiction, [ 11 C]raclopride and [ 11 C]‐(+)‐PHNO PET revealed no differences in dopamine receptor DRD2/3 availability and greater stimulant‐induced dopamine release in individuals with GD compared with healthy volunteers (HV; Albein‐Urios et al 2012a,2012b; Boileau et al 2013; Boileau et al 2014). A key modulator of the dopaminergic system is the mu opioid receptor (MOR), and opiate receptor antagonists have some efficacy in treating GD.…”

Section: Introductionmentioning

confidence: 75%

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

et al. 2016

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As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAA receptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15‐4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11C]Ro15‐4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of the ‘Negative Urgency’ construct of impulsivity in GD, and these were positively associated with higher [11C]Ro15‐4513 VT in the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAA receptors in GD with [11C]Ro15‐4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.

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Section: Introductionmentioning

confidence: 75%

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

et al. 2016

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“…In particular, PET studies have shown enhanced amphetamine-and gambling-induced dopamine release in the striatum of individuals with pathological gambling symptoms, as compared with healthy controls (Boileau et al, 2014;Steeves et al, 2009). Dopamine D3 receptor binding in the substantia nigra was also shown to be positively correlated with gambling severity (Boileau et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

Sescousse

Janssen

Hashemi

et al. 2016

Neuropsychopharmacol

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Near-misses in gambling games are losing events that come close to a win. Near-misses were previously shown to recruit reward-related brain regions including the ventral striatum, and to invigorate gambling behavior, supposedly by fostering an illusion of control. Given that pathological gamblers are particularly vulnerable to such cognitive illusions, their persistent gambling behavior might result from an amplified striatal sensitivity to near-misses. In addition, animal studies have shown that behavioral responses to near-miss-like events are sensitive to dopamine, but this dopaminergic influence has not been tested in humans. To investigate these hypotheses, we recruited 22 pathological gamblers and 22 healthy controls who played a slot machine task delivering wins, near-misses and full-misses, inside an fMRI scanner. Each participant played the task twice, once under placebo and once under a dopamine D2 receptor antagonist (sulpiride 400 mg), in a doubleblind, counter-balanced design. Participants were asked about their motivation to continue gambling throughout the task. Across all participants, near-misses elicited higher motivation to continue gambling and increased striatal responses compared with full-misses. Crucially, pathological gamblers showed amplified striatal responses to near-misses compared with controls. These group differences were not observed following win outcomes. In contrast to our hypothesis, sulpiride did not induce any reliable modulation of brain responses to near-misses. Together, our results demonstrate that pathological gamblers have amplified brain responses to near-misses, which likely contribute to their persistent gambling behavior. However, there is no evidence that these responses are influenced by dopamine. These results have implications for treatment and gambling regulation. INTRODUCTIONPathological gambling is a behavioral addiction with dramatic consequences including bankruptcy, unemployment, and relationship problems. The prevalence among college students has risen sharply in the past 10 years (Nowak and Aloe, 2014), while the rate of attempted suicide, approaching 20%, is higher than for any other addictive disorder (Bischof et al, 2015). Central to pathological gambling is the loss of control over gambling behavior and the inability to stop playing. This compulsive behavior is postulated to be fueled by cognitive distortions regarding the game structure. One example is the misappraisal of nearmiss events-losing outcomes that come close to a winwhich invigorate ongoing gambling behavior, conceivably by fostering an illusion of control (Clark, 2010). Although the behavioral vulnerability of pathological gamblers to such cognitive distortions is well established (Michalczuk et al, 2011), the underlying neural and neurochemical mechanisms remain elusive. We aimed to address this question using a combination of fMRI and pharmacological manipulation.Near-miss events are a hallmark of many gambling games and are particularly frequent in slot machines, which are recogniz...

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“…Compared with healthy controls, individuals with pathological gambling also exhibit greater DA release (54%-63%) in the striatum and midbrain in response to an oral amphetamine challenge. 14 Using locomotor activity following a low dose of amphetamine as a noninvasive, indirect correlate of mesolimbic DA sensitization, recent studies have shown that repeated expos ure to unpredictable reward delivery 15 or responding for reinforcement on a variable schedule of reward delivery enhanced amphetamine's ability to increase locomotor activity compared with control groups. As a result, both repeated exposure to psychostimulants and uncertainty expos ure (UE) appear to induce a similar behavioural response that likely reflects DA sensitization.…”

Section: Introductionmentioning

confidence: 99%

Uncertainty exposure causes behavioural sensitization and increases risky decision-making in male rats: toward modelling gambling disorder

Zeeb

Fisher

et al. 2017

JPN

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In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO

Cited by 180 publications

References 75 publications

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

Uncertainty exposure causes behavioural sensitization and increases risky decision-making in male rats: toward modelling gambling disorder

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