What is the role of the D3 receptor in addiction? A mini review of PET studies with [11C]-(+)-PHNO

Payer, Doris; Balasubramaniam, Gayathiri; Boileau, Isabelle

doi:10.1016/j.pnpbp.2013.08.012

Cited by 43 publications

(43 citation statements)

References 68 publications

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“…Initial evidence for the role of dopamine in PG came from the clinical observation that a subset of patients with Parkinson's disease develop PG symptoms after receiving dopaminergic replacement therapy, in particular dopamine D 2 /D 3 receptor agonists with high affinity for D 3 receptors (Voon et al, 2009; Seeman, 2015). This concurs with recent evidence showing that PG is characterized by a hyper-dopaminergic state (Boileau et al, 2014; van Holst et al, 2017), and the prominent role of dopamine D 3 receptors in human and rat models of PG (Payer et al, 2014; Lobo et al, 2015). However, the specific mechanisms through which dopamine D 2 /D 3 receptor activity may act to foster PG remain elusive.…”

Section: Introductionsupporting

confidence: 92%

Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

Ojala¹,

Janssen²,

Hashemi³

et al. 2018

eNeuro

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Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioral addiction characterized by excessive risk-taking behavior. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighting during decision making. Human healthy controls (n = 21) and pathological gamblers (n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D2/D3 receptor antagonist sulpiride, in a double-blind counterbalanced design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e., they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although gamblers consistently underweighted losing probabilities in the placebo condition. Overall, our results reveal that dopamine D2/D3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision making.

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Section: Introductionsupporting

confidence: 92%

Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

Ojala¹,

Janssen²,

Hashemi³

et al. 2018

eNeuro

View full text Add to dashboard Cite

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“…Imaging studies have shown that the D 3 R are higher (Prayer et al, 2014; Boileau et al, 2012) and the D 2 R are lower (Volkow et al, 1990, 2001; Nader et al, 2006; Prayer et al, 2014) following both chronic cocaine and MA exposure, although it is not possible to directly compare the magnitude of the differences between studies. While the magnitude of change between D 2 R and D 3 R availability and density could be different following chronic cocaine vs. MA exposure, differences in D 2 /D 3 R sensitivity may be the more likely mechanism, especially considering there were significant differences in the efficacy of quinpirole to elicit yawns between groups, with MA monkeys being more sensitive to quinpirole (Martelle et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of the dopamine D3 receptor antagonist PG01037 on cocaine and methamphetamine self-administration in rhesus monkeys

2015

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The dopamine D3 receptor (D3R) has been shown to mediate many of the behavioral effects of psychostimulants associated with high abuse potential. This study extended the assessment of the highly selective D3R antagonist PG01037 on cocaine and methamphetamine (MA) self-administration to include a food-drug choice procedure. Eight male rhesus monkeys (n=4/group) served as subjects in which complete cocaine and MA dose-response curves were determined daily in each session. When choice was stable, monkeys received acute and five-day treatment of PG01037 (1.0–5.6 mg/kg, i.v.). Acute administration of PG01037 was effective in reallocating choice from cocaine to food and decreasing cocaine intake, however, tolerance developed by day 5 of treatment. Up to doses that disrupted responding, MA choice and intake were not affected by PG01037 treatment. PG01037 decreased total reinforcers earned per session and the behavioral potency was significantly greater on MA-food choice compared to cocaine-food choice. Furthermore, the acute efficacy of PG01037 was correlated with the sensitivity of the D3/D2R agonist quinpirole to elicit yawning. These data suggest (1) that efficacy of D3R compounds in decreasing drug choice is greater in subjects with lower D3R, perhaps suggesting that it is percent occupancy that is the critical variable in determining efficacy and (2) differences in D3R activity in chronic cocaine vs. MA users. Although tolerance developed to the effects of PG01037 treatment on cocaine choice, tolerance did not develop to the disruptive effects on food-maintained responding. These findings suggest that combination treatments that decrease cocaine-induced elevations in DA may enhance the efficacy of D3R antagonists on cocaine self-administration.

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“…In patients with Parkinson’s disease intensive exercise leads to increased D 2 -type receptor BP ND (Fisher et al, 2013), and preliminary findings suggest a positive finding in methamphetamine users as well (Robertson et al, 2013). Future studies may also benefit from therapeutic approaches targeted at novel targets in the dopamine system, such as the D3 receptor (Baladi et al, 2014; Paterson et al, 2014), as chronic methamphetamine exposure is associated with reduced levels of D 2 receptors but elevated levels of D 3 receptors (Boileau et al, 2012; Payer et al, 2014). …”

Section: Implications For Therapymentioning

confidence: 99%

Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging

et al. 2015

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Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets.

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What is the role of the D3 receptor in addiction? A mini review of PET studies with [11C]-(+)-PHNO

Cited by 43 publications

References 68 publications

Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

Differential effects of the dopamine D3 receptor antagonist PG01037 on cocaine and methamphetamine self-administration in rhesus monkeys

Chronic methamphetamine abuse and corticostriatal deficits revealed by neuroimaging

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