Commentary on <scp>B</scp>oileau <i>et al</i>. (2013): Distinguishing <scp>D2/D3</scp> dopaminergic contributions to addictions

Potenza, Marc N.; Brody, Arthur L.

doi:10.1111/add.12119

Cited by 6 publications

(4 citation statements)

References 20 publications

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“…The role played by striatal DA signaling in GD, however, seems more complex than in SUD. While a lower density of D 2/3 receptors within the ventral striatum has been repeatedly observed in SUD populations (Volkow et al, 2009), data from GD subjects have been more equivocal (Clark et al, 2012;Potenza and Brody, 2013;Sescousse et al, 2016). Although data suggest those with GD have elevated DA synthesis capacity within the ventral striatum (van Holst et al, 2018), this population also shows blunted ventral striatum activation during reward anticipation (Luijten et al, 2017).…”

Section: Discussionmentioning

confidence: 87%

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction

Ferland¹,

Hynes²,

Hounjet³

et al. 2019

J. Neurosci.

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Rats trained to perform a version of the rat gambling task (rGT) in which salient audiovisual cues accompany reward delivery, similar to commercial gambling products, show greater preference for risky options. Given previous demonstrations that probabilistic reinforcement schedules can enhance psychostimulant-induced increases in accumbal DA and locomotor activity, we theorized that performing this cued task could perpetuate a proaddiction phenotype. Significantly more rats developed a preference for the risky options in the cued versus uncued rGT at baseline, and this bias was further exacerbated by cocaine self-administration, whereas the choice pattern of optimal decision-makers was unaffected. The addition of reward-paired cues therefore increased the proportion of rats exhibiting a maladaptive cognitive response to cocaine self-administration. Risky choice was not associated with responding for conditioned reinforcement or a marker of goal/sign-tracking, suggesting that reward-concurrent cues precipitate maladaptive choice via a unique mechanism unrelated to simple approach toward, or responding for, conditioned stimuli. Although "protected" from any resulting decision-making impairment, optimal decision-makers trained on the cued rGT nevertheless self-administered more cocaine than those trained on the uncued task. Collectively, these data suggest that repeated engagement with heavily cued probabilistic reward schedules can drive addiction vulnerability through multiple behavioral mechanisms. Rats trained on the cued rGT also exhibited blunted locomotor sensitization and lower basal accumbal DA levels, yet greater cocaine-induced increases in accumbal DA efflux. Gambling in the presence of salient cues may therefore result in an adaptive downregulation of the mesolimbic DA system, rendering individuals more sensitive to the deleterious effects of taking cocaine. Impaired cost/benefit decision making, exemplified by preference for the risky, disadvantageous options on the Iowa Gambling Task, is associatedwithgreaterriskofrelapseandtreatmentfailureinsubstanceusedisorder.Understandingfactorsthatenhancepreferencefor risk may help elucidate the neurobiological mechanisms underlying maladaptive decision making in addiction, thereby improving treatment outcomes. Problem gambling is also highly comorbid with substance use disorder, and many commercial gambling products incorporate salient win-paired cues. Here we show that adding reward-concurrent cues to a rat analog of the IGT precipitates a hypodopaminergic state, characterized by blunted accumbal DA efflux and attenuated locomotor sensitization, which may contribute to the enhanced responsivity to uncertain rewards or the reinforcing effects of cocaine we observed.

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Section: Discussionmentioning

confidence: 87%

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction

Ferland¹,

Hynes²,

Hounjet³

et al. 2019

J. Neurosci.

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“…We suggest that understanding of normative decision-making processes and their neural bases is fundamental to understanding what “goes wrong” in psychopathological conditions. The challenge for future studies will be to work towards establishing an integrative framework, perhaps using dual radiotracer approaches that allow evaluation of detailed associations between neurotransmitter systems (Potenza and Brody 2013), to explore the involvement of mesocortical DA pathways and interrelationships between VS and PFC DA systems. Additional research is also needed to tease apart the various components of risk-taking and to evaluate the clinical implications of the findings, particularly with respect to addictive behaviors.…”

Section: 0 Discussionmentioning

confidence: 99%

Risky decision-making and ventral striatal dopamine responses to amphetamine: A positron emission tomography [11C]raclopride study in healthy adults

et al. 2015

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Recent functional magnetic resonance imaging (fMRI) studies have provided compelling evidence that corticolimbic brain regions are integrally involved in human decision-making. Although much less is known about molecular mechanisms, there is growing evidence that the mesolimbic dopamine (DA) neurotransmitter system may be an important neural substrate. Thus far, direct examination of DA signaling in human risk-taking has centered onl gambling disorder. Findings from several positron emission tomography (PET) studies suggest that dysfunctions in mesolimbic DA circuits may play an important role in gambling behavior. Nevertheless, interpretation of these findings is currently hampered by a need for better understanding of how individual differences in regional DA function influence normative decision-making in humans. To further our understanding of these processes, we used [11C]raclopride PET to examine associations between ventral striatal (VS) DA responses to amphetamine (AMPH) and risky decision-making in a sample of healthy young adults with no history of psychiatric disorder, Forty-five male and female subjects, ages 18–29 years, completed a computerized version of the IOWA Gambling Task. Participants then underwent two 90-minute PET studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second, by intravenous AMPH (0.3 mg/kg). Findings of primary analyses showed that less advantageous decision-making was associated with greater right VS DA release; the relationship did not differ as a function of gender. No associations were observed between risk-taking and left VS DA release or baseline D2/D3 receptor availability in either hemisphere. Overall, the results support notions that variability in striatal DA function may mediate inter-individual differences in risky decision-making in healthy adults, further suggesting that hypersensitive DA circuits may represent a risk pathway in this population.

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“…Similarly, no between-group difference between PG and comparison subjects was observed using [ 11 C]raclopride or the D3-preferring agonist-radioligand [ 11 C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) (Boileau et al, 2013 ). However, in these studies, relationships with mood-related or generalized impulsivity, disadvantageous decision-making or problem-gambling severity were reported, suggesting that dopamine function may relate to specific aspects of PG (Potenza and Brody, 2013 ). These findings are consistent with the idea that PG represents a heterogeneous condition and that identifying biologically relevant individual differences or subgroups may help advance treatment development or the appropriate targeting of therapeutic interventions.…”

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confidence: 99%

How central is dopamine to pathological gambling or gambling disorder?

Potenza

2013

Front. Behav. Neurosci.

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Commentary on Boileau et al. (2013): Distinguishing D2/D3 dopaminergic contributions to addictions

Cited by 6 publications

References 20 publications

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction

Prior Exposure to Salient Win-Paired Cues in a Rat Gambling Task Increases Sensitivity to Cocaine Self-Administration and Suppresses Dopamine Efflux in Nucleus Accumbens: Support for the Reward Deficiency Hypothesis of Addiction

Risky decision-making and ventral striatal dopamine responses to amphetamine: A positron emission tomography [11C]raclopride study in healthy adults

How central is dopamine to pathological gambling or gambling disorder?

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