Alcohol-Paired Contextual Cues Produce an Immediate and Selective Loss of Goal-directed Action in Rats

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles Los Angeles, CA, USA.
Frontiers in Integrative Neuroscience 07/2010; 4. DOI: 10.3389/fnint.2010.00019
Source: PubMed

ABSTRACT We assessed whether the presence of contextual cues paired with alcohol would disrupt rats' capacity to express appropriate goal-directed action control. Rats were first given differential context conditioning such that one set of contextual cues was paired with the injection of ethanol and a second, distinctive set of cues was paired with the injection of saline. All rats were then trained in a third, neutral context to press one lever for grain pellets and another lever for sucrose pellets. They were then given two extinction tests to evaluate their ability to choose between the two actions in response to the devaluation of one of the two food outcomes with one test conducted in the alcohol-paired context and the other conducted in the control (saline-paired) context. In the control context, rats exhibited goal-directed action control; i.e., they were able selectively to withhold the action that previously earned the now devalued outcome. However, these same rats were impaired when tested in the alcohol-paired context, performing both actions at the same rate regardless of the current value of their respective outcomes. Subsequent testing revealed that the rats were capable of overcoming this impairment if they were giving response-contingent feedback about the current value of the food outcomes. These results provide a clear demonstration of the disruptive influence that alcohol-paired cues can exert on decision-making in general and goal-directed action selection and choice in particular.

Download full-text


Available from: Bernard W Balleine, Aug 25, 2015
  • Source
    • "By contrast, participants in the water expectancy group saw the experimenter pour a standard glass (284 ml) of bottled water, which was placed by the participant with the instructions that they could drink this after the computer task was finished. The aim of this design was to generate effective alcohol expectancy arguably akin to rats in Ostlund et al. (2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The transition from goal-directed to habitual control over drug-seeking has been experimentally demonstrated in animals, but there have been no comparable reports in humans. Following a recent animal design, the current study employed an outcome-devaluation procedure to test whether goal-directed control over tobacco seeking would be abolished by alcohol expectancy. Eighty smokers first learned that two responses earned tobacco or chocolate points, respectively, before tobacco was devalued by health warnings and smoking satiety. Participants were then presented with either a glass of beer/wine or water with instructions that this item could be consumed after the task (alternative reward). Then choice between the tobacco and chocolate response was measured in extinction to assess goal-directed control of tobacco seeking, in a nominal Pavlovian to instrumental transfer (PIT) test to assess stimulus control of tobacco seeking, and in a reacquisition test to assess the impact of direct feedback from the outcomes. The results showed that alcohol expectancy selectively abolished goal-directed control of tobacco seeking but not stimulus control or the impact of feedback from outcomes. These data suggest that 'endogenous' retrieval of low drug value governing goal-directed regulation of drug seeking is disrupted by conflicting appraisal of an alternative reinforcer, promoting habitual control, which may play a role in relapse.
    Addiction Biology 11/2012; 18(1):1-19. DOI:10.1111/adb.12009 · 5.93 Impact Factor
  • Source
    • "Response acquisition deficits may be attributable to an inability to modify response strategies in the presence of reward-associated conditioned stimuli (for discussion, see Ostlund et al., 2010). Thus, we trained mice to respond for food reinforcers accompanied by an auditory tone signaling food delivery. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adolescence is characterized by vulnerability to the development of neuropsychiatric disorders including drug addiction, as well as prefrontal cortical refinement that culminates in structural stability in adulthood. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, although intracellular mechanisms are largely unknown. We characterized layer V prefrontal dendritic spine development and refinement in adolescent wild-type mice and mice lacking the cytoskeletal regulatory protein Abl-related gene (Arg) kinase. Relative to hippocampal CA1 pyramidal neurons, which exhibited a nearly linear increase in spine density up to postnatal day 60 (P60), wild-type prefrontal spine density peaked at P31, and then declined by 18% by P56-P60. In contrast, dendritic spines in mice lacking Arg destabilized by P31, leading to a net loss in both structures. Destabilization corresponded temporally to the emergence of exaggerated psychomotor sensitivity to cocaine. Moreover, cocaine reduced dendritic spine density in wild-type orbitofrontal cortex and enlarged remaining spine heads, but arg(-/-) spines were unresponsive. Local application of Arg or actin polymerization inhibitors exaggerated cocaine sensitization, as did reduced gene dosage of the Arg substrate, p190RhoGAP. Genetic and pharmacological Arg inhibition also retarded instrumental reversal learning and potentiated responding for reward-related cues, providing evidence that Arg regulates both psychomotor sensitization and decision-making processes implicated in addiction. These findings also indicate that structural refinement in the adolescent orbitofrontal cortex mitigates psychostimulant sensitivity and support the emerging perspective that the structural response to cocaine may, at any age, have behaviorally protective consequences.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 02/2012; 32(7):2314-23. DOI:10.1523/JNEUROSCI.2730-11.2012 · 6.75 Impact Factor
  • Source
    • "Konsumiert eine solche Person z.B. mehrere Tafeln Schokolade, wird ihr die Schokolade hinterher unattraktiv erscheinen und sie wird sich für das alternative Nahrungsmittel entscheiden. Dies ist aber offenbar dann nicht der Fall, wenn die Person vor oder nach dem Lernvorgang unter Stress stand oder wenn es sich um Alkohol konsumierende Tiere handelte, welche jetzt erneut in der Umgebung getestet werden, in der sie früher Alkohol getrunken haben (Ostlund et al. 2010, Schwabe und Wolf 2010). Dies zeigt, dass beim Verlernen – in diesem Fall der Vorliebe für eine präferierte Nahrungssubstanz – Stress wie Alkoholkonsum offenbar eine störende Rolle ausüben können. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Zusammenfassung Verschiedene Studien zur Alkoholabhängigkeit zeigen, dass Lern-mechanismen nicht nur dann eine Rolle spielen, wenn ein Individuum sich an den zunehmenden Alkoholkonsum gewöhnt. Vielmehr scheinen Lernmechanismen auch bei der Aufrechterhaltung abhängigen Verhal-tens eine entscheidende Rolle zu spielen; zu nennen ist hier die Schwie-rigkeit, einmal gelerntes Verhalten wieder zu "verlernen". Ein klinisches Beispiel ist durch einen alkoholabhängigen Patienten gegeben, welcher schon lange beim Konsum seines Lieblingsgetränks nur noch wenig Freu-de empfindet, sich aber trotzdem nur schwer zurückhalten kann, wenn ihm ein solches Getränk angeboten wird. Eine starke Reaktion auf alkohol-bezogene Reize in Zentren des Belohnungssystems schient hier eine Rolle zu spielen, welche sich mehr oder weniger automatisch dem be-troffenen Individuum aufdrängt und es motiviert, diese nicht mehr als attraktiv erlebte Substanz erneut zu konsumieren. Umgekehrt scheinen Patienten in ihrer Fähigkeit, neue, nicht alkoholbezogene Verhaltens-weisen zu erlernen, durchaus individuell unterschiedlich stark beein-trächtigt zu sein, was wiederum mit alkoholbezogenen Funktionsstö-rungen des Belohnungssystems zusammenhängt. Patienten haben also Schwierigkeiten, etwas Neues zu lernen, und Geduld wie Verständnis vonseiten der Therapeuten und ihrer Umwelt ist gerade bei den schwe-rer beeinträchtigten Mitmenschen gefordert. Abstract Beitragstitel bitte ebenfalls übersetzen. Danke! Studies investigating alcohol consumption and dependence demon-strate that learning mechanisms play a crucial role not only in subjects with increased alcohol intake, but also in patients suffering from mani-fest dependence. Hereby, patients appear to display impairments in "unlearning" previous established behaviour associated with alcohol intake. This can be seen in clinical every day life, where alcohol dependent patients are no longer enjoying the favoured alcoholic beverage al-though they can hardly resist the urge to drink. A strong and more or less automatic response in the neuronal reward system on alcohol-associated cues appears to motivate the subjects towards the consumption of this subjectively unappealing drug. Impaired abilities to learn and establish new and alcohol-unrelated behaviour patterns also relate to functional deficits of the reward system. Therapeutic approaches may have to take these impairments into account, which also remind us to show patience and understanding towards alcohol dependent patients.
    Suchtmedizin in Forschung und Praxis 01/2011; 13(131).
Show more