Association of the <i>OPRM1</i> A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Sebold, Miriam; Garbusow, Maria; Cerci, Deniz; Chen, Ke; Sommer, Christian; Huys, Quentin J. M.; Nebe, Stephan; Rapp, Michael A.; Veer, Ilya M.; Zimmermann, U.; Smolka, Michael N.; Walter, Henrik; Heinz, Andreas; Friedel, Eva

doi:10.1177/0269881121991992

Cited by 12 publications

(11 citation statements)

References 82 publications

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“…This influence seems to serve an adaptive function by promoting risky and effortful foraging activity in environments that signal potential reward availability. The PIT paradigm is widely used to study the mechanisms of cue-motivated behavior (Cartoni et al, 2016; Corbit & Balleine, 2016) and how they contribute to pathological reward seeking in addiction and related disorders (Corbit & Janak, 2007, 2016; Garbusow et al, 2016; Genauck et al, 2020; LeBlanc et al, 2012, 2013, 2014; Marshall & Ostlund, 2018; Ostlund et al, 2014; Saddoris et al, 2011; Sebold et al, 2021; Shiflett, 2012; Shiflett et al, 2013; Vogel et al, 2018; Wyvell & Berridge, 2001). However, despite decades of research, much remains unclear about how fundamental variables such as expected reward value influence expression of the PIT effect.…”

mentioning

confidence: 99%

Flexible control of Pavlovian-instrumental transfer based on expected reward value.

Marshall¹,

Halbout²,

Munson³

et al. 2023

Journal of Experimental Psychology: Animal Learning and Cogniti

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The Pavlovian-instrumental transfer (PIT) paradigm is widely used to assay the motivational influence of reward-predictive cues, reflected by their ability to invigorate instrumental behavior. Leading theories assume that a cue's motivational properties are tied to predicted reward value. We outline an alternative view that recognizes that reward-predictive cues may suppress rather than motivate instrumental behavior under certain conditions, an effect termed positive conditioned suppression. We posit that cues signaling imminent reward delivery tend to inhibit instrumental behavior, which is exploratory by nature, in order to facilitate efficient retrieval of the expected reward. According to this view, the motivation to engage in instrumental behavior during a cue should be inversely related to the value of the predicted reward, since there is more to lose by failing to secure a high-value reward than a low-value reward. We tested this hypothesis in rats using a PIT protocol known to induce positive conditioned suppression. In Experiment 1, cues signaling different reward magnitudes elicited distinct response patterns. Whereas the one-pellet cue increased instrumental behavior, cues signaling three or nine pellets suppressed instrumental behavior and elicited high levels of food-port activity. Experiment 2 found that reward-predictive cues suppressed instrumental behavior and increased food-port activity in a flexible manner that was disrupted by post-training reward devaluation. Further analyses suggest that these findings were not driven by overt competition between the instrumental and food-port responses. We discuss how the PIT task may provide a useful tool for studying cognitive control over cue-motivated behavior in rodents.

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mentioning

confidence: 99%

Flexible control of Pavlovian-instrumental transfer based on expected reward value.

Marshall¹,

Halbout²,

Munson³

et al. 2023

Journal of Experimental Psychology: Animal Learning and Cogniti

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“…Interestingly, on a neural level, these PIT effects are associated with increased neural activity in the ventral striatum [180], thus suggesting a potential neurobiological correlate. Furthermore, a genetic polymorphism of the opioid system, which has also been associated with treatment response to naltrexone [183], is related to the behavioral expression of the PIT effect [184]. These studies further suggest that the biological and cognitive mechanisms that are related to the addiction cycle might serve as a potential target for pharmacological treatment stratification of AUD.…”

Section: Limitationsmentioning

confidence: 78%

Computational Theories of Alcohol Use Disorder: Mapping Learning and Choice Mechanisms on Symptoms

et al. 2022

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Alcohol use disorder (AUD) is characterized by a combination of symptoms including excessive craving, loss of control, and progressive neglect of alternative pleasures. A mechanistic understanding of what drives these symptoms is needed to improve diagnostic stratification and to develop new treatment and prevention strategies for AUD. To date, there is no consensus regarding a unifying mechanistic framework that accounts for the different symptoms of AUD. Reinforcement learning (RL) and economic choice theories may be key to elucidating the underlying processes of symptom development and maintenance in AUD. These algorithms may account for the different behavioral and physiological phenomena and are suited to dissect mechanisms linked to different symptoms of AUD. We here review different RL and economic choice models and how they map onto three symptoms of AUD: (1) cue-induced craving, (2) neglect of alternative rewards, and (3) consumption despite adverse consequences. For each symptom and theory, we describe findings from animal and human studies. In humans, we focus on empirical studies that investigated RL models in the context of treatment outcome in AUD. The review indicates important gaps to be addressed in the future by highlighting the challenges in transferring findings from RL and economic choice studies to clinical application. We also critically evaluate the potential and pitfalls of a symptom-oriented approach and highlight the importance of elucidating the role of learning and decision-making processes across diagnostic boundaries.

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“…Sebold et al [36] further investigated potential biomarkers for the wanting of drug-related cues according to the incentive-sensitization theory [14]. They investigated the A118G polymorphism of the OPRM1 gene, money-related PIT, and relapse rates in recently detoxified AD patients, as well as two independent HC samples.…”

Section: Pit Across Mental Disordersmentioning

confidence: 99%

Pavlovian-to-Instrumental Transfer across Mental Disorders: A Review

et al. 2022

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A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.

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Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Cited by 12 publications

References 82 publications

Flexible control of Pavlovian-instrumental transfer based on expected reward value.

Flexible control of Pavlovian-instrumental transfer based on expected reward value.

Computational Theories of Alcohol Use Disorder: Mapping Learning and Choice Mechanisms on Symptoms

Pavlovian-to-Instrumental Transfer across Mental Disorders: A Review

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