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      Does acute stress influence the Pavlovian-to-instrumental transfer effect? Implications for substance use disorders

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          Abstract

          Rational

          The ability of conditioned stimuli to affect instrumental responding is a robust finding from animal as well as human research and is assumed as a key factor regarding the development and maintenance of addictive behaviour.

          Objectives

          While it is well known that stress is an important factor for relapse after treatment, little is known about the impact of stress on conditioned substance-associated stimuli and their influence on instrumental responding.

          Methods

          We administered in the present study a Pavlovian-to-instrumental transfer (PIT) paradigm with stimuli associated with smoking- and chocolate-related rewards using points in a token economy to light to moderate smokers who also indicated to like eating chocolate. After completion of the first two phases of the PIT paradigm (i.e. Pavlovian training and instrumental trainings), participants were randomly allocated to the socially evaluated cold pressor test or a control condition before the final phase of the PIT paradigm, the transfer phase, was administered.

          Results

          The presentation of a smoking-related stimulus enhanced instrumental responding for a smoking-related reward (i.e. ‘smoking-PIT’ effect) and presentation of a chocolate-related stimulus for a chocolate-related reward (i.e. ‘chocolate-PIT’ effect) in participants aware of the experimental contingencies as indicated by expectancy ratings. However, acute stress did not change (i.e. neither enhanced nor attenuated) the ‘smoking-PIT’ effect or the ‘chocolate-PIT’ effect, and no overall effect of acute stress on tobacco choice was observed in aware participants.

          Conclusions

          The established role of stress in addiction appears not to be driven by an augmenting effect on the ability of drug stimuli to promote drug-seeking.

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          Most cited references52

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          Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On.

          A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use.
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            A role for brain stress systems in addiction.

            Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take drugs and has been linked to dysregulation of brain regions that mediate reward and stress. Activation of brain stress systems is hypothesized to be key to the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms. This review explores the role of brain stress systems (corticotropin-releasing factor, norepinephrine, orexin [hypocretin], vasopressin, dynorphin) and brain antistress systems (neuropeptide Y, nociceptin [orphanin FQ]) in drug dependence, with emphasis on the neuropharmacological function of extrahypothalamic systems in the extended amygdala. The brain stress and antistress systems may play a key role in the transition to and maintenance of drug dependence once initiated. Understanding the role of brain stress and antistress systems in addiction provides novel targets for treatment and prevention of addiction and insights into the organization and function of basic brain emotional circuitry.
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              Classification criteria for distinguishing cortisol responders from nonresponders to psychosocial stress: evaluation of salivary cortisol pulse detection in panel designs.

              Hypothalamic-pituitary-adrenal axis reactivity to acute stimulation is frequently assessed by repeated sampling of salivary cortisol. Researchers often strive to distinguish between individuals who show (responders) and those do not show (nonresponders) cortisol responses. For this, fixed threshold classification criteria, such as a 2.5-nmol/l baseline-to-peak increase, are frequently used. However, the performance of such criteria has not been systematically evaluated. Repeated salivary cortisol data from 504 participants exposed to either the Trier Social Stress Test (TSST; n = 309) or a placebo protocol (n = 195) were used for analyses. To obtain appropriate classifications of cortisol responders versus nonresponders, a physiologically plausible, autoregressive latent trajectory (ALT) mixture model was fitted to these data. Response classifications according to the ALT model and information on the experimental protocol (TSST versus placebo TSST) were then used to evaluate the performance of different proposed classifier proxies by receiver operating characteristics. Moment structure of cortisol time series was adequately accounted for by the proposed ALT model. The commonly used 2.5-nmol/l criterion was found to be overly conservative, resulting in a high rate of 16.5% false-negative classifications. Lowering this criterion to 1.5 nmol/l or using a percentage baseline-to-peak increase of 15.5% as a threshold yielded improved performance (39.3% and 26.7% less misclassifications, respectively). Alternative classification proxies (1.5 nmol/l or 15.5% increase) are able to effectively distinguish between cortisol responders and nonresponders and should be used in future research, whenever statistical response class allocation is not feasible.
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                Author and article information

                Contributors
                sabine.steins-loeber@uni-bamberg.de
                Journal
                Psychopharmacology (Berl)
                Psychopharmacology (Berl.)
                Psychopharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0033-3158
                1432-2072
                6 June 2020
                6 June 2020
                2020
                : 237
                : 8
                : 2305-2316
                Affiliations
                [1 ]GRID grid.7359.8, ISNI 0000 0001 2325 4853, Department of Clinical Psychology and Psychotherapy, , Otto-Friedrich-University of Bamberg, ; Markusplatz 3, 96047 Bamberg, Germany
                [2 ]GRID grid.10423.34, ISNI 0000 0000 9529 9877, Department of Psychosomatic Medicine and Psychotherapy, , Hannover Medical School, ; Hannover, Germany
                [3 ]GRID grid.5718.b, ISNI 0000 0001 2187 5445, Department of General Psychology: Cognition, , University of Duisburg-Essen, ; Duisburg, Germany
                [4 ]GRID grid.12082.39, ISNI 0000 0004 1936 7590, Sussex Addiction Research and Intervention Centre, School of Psychology, , University of Sussex, ; Brighton, UK
                [5 ]GRID grid.5570.7, ISNI 0000 0004 0490 981X, Department of Cognitive Psychology, , Ruhr University Bochum, ; Bochum, Germany
                Author information
                http://orcid.org/0000-0002-7651-0627
                Article
                5534
                10.1007/s00213-020-05534-8
                7351872
                32506233
                bed99bf2-17fe-44af-a7ec-b3e815d288da
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 December 2019
                : 22 April 2020
                Funding
                Funded by: Otto-Friedrich-Universität Bamberg (3120)
                Categories
                Original Investigation
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Pharmacology & Pharmaceutical medicine
                addiction,nicotine dependence,socially evaluated cold pressor test

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