Training that is performed to teach individuals to predict a negative outcome following a stimulus. This is done by repeatedly presenting an individual with a negative outcome following stimulation.

It has been found that cocaine users and their non–drug using siblings both had a deficit in response control. Siblings who were not exposed to cocaine showed a deficit in response control and similar changes in brain regions as their cocaine-using counterparts.

This suggests that there are inherent traits such as impulsivity and poor inhibitory control that are caused by differences in brain physiology. This means that even before someone starts taking drugs, they may be vulnerable to drug addiction.

It is possible that siblings of drug-dependent people have other traits that protect them from being vulnerable to drug addiction, i.e. traits making them less likely to start seeking drugs in the first place. This suggests that changes in brain physiology in drug-dependent people are not all cocaine-induced, and that there are some heritable (both genetically and epigenetically) differences in brain structure and function that can predispose people to addiction.

A positive or negative inclination toward something.

CUD patients continued to respond to stimuli that were previously associated with a reward, even after the association with the reward was removed.

Further, when the behavior became more habitual and less goal-oriented, they showed an increased response rate to the stimuli. This persisted even after the reward was removed.

Cocaine use disorder (CUD) patients were not as successful as control volunteers in learning which animal pictures gained them points and which associated with electric shocks.

Acronym for standard error of the mean, a measure that represents how far the mean of a sample is from the estimated true population mean. It is a good estimate of how accurately your mean reflects the true population.

To learn more about SEM: https://www.khanacademy.org/math/ap-statistics/sampling-distribution-ap/sampling-distribution-mean/v/standard-error-of-the-mean

An analysis of covariance is used to see how two independent variables change together.

Here, the authors used it to determine whether the response to a reward or devaluated stimuli was due to habitual learning, rather than external factors such as outcome-action knowledge, working-memory/inhibition, or the ability to learn how to discriminate during the training phase of the test.

To learn more about analysis of covariance: http://www.lehigh.edu/~wh02/ancova.html

Previous work has looked at how the decision-making process informs goal-directed behaviors. The systems that govern goal-directed behaviors and habitual behaviors are spread across the corticostriatal regions of the brain.

Normally, these two systems operate in parallel (at the same time, but not necessarily together). With extended training or repetition of a specific behavior or use of stimulant drugs, the habit system can start to play a larger role over behavior and diminish the role of the goal-directed system.

Once a behavior (like drug-seeking) has become habitual, the behavior will still occur even when the reward is removed (e.g., when the effects of the drug no longer feel good).

Internal or external changes in the environment that elicit an action.

An object used for drug use, production, or storage.

For a summary of this article, see lead author Dr. Karen Ersche's story on the UK Medical Research Council's website:

http://www.insight.mrc.ac.uk/2016/06/16/breaking-the-habit-why-is-it-so-difficult-to-change-cocaine-users-behaviour/

Ersche et al. studied the brain structure and behavior control capacities of 50 sibling pairs where one of the siblings was considered drug dependent, and compared them with 50 volunteer controls. The authors found that both siblings had deficits in regulating behavior with brain structure. They saw a reduction of white matter in drug dependent individuals and their biological siblings, which may predispose to drug use and indicate a genetic component to drug dependency..

In this study, Miles et al. were interested in looking at how chronic cocaine use in rats affects response to outcome devaluation. His group noted that chronic cocaine users were not responsive to changes.

Beninger et al. studied the effect of pimozide treatment, a dopamine receptor blocker, to determine if treated rats would avoid the negative outcomes that were previously associated with a particular stimulus.

They found that treated animals could not avoid the negative outcomes due to their inability to initiate a response to the stimulus.

CUD patients may be at risk of developing habitual behavior due to their impairment in action-control behaviors.

The fact that CUD patients respond equally to pictures associated with values and those without an association suggests that they can no longer control their actions.

These reactions could indicate habitual behaviors, putting them at risk for compulsive behaviors.

Compounds derived from a plant known as the opium poppy. Originally these came only from natural sources, but now there are synthetic opioids. They are often prescribed for pain relief.

Opiates are considered controlled substances due to their addictive properties. One example is heroin.

In one study, researchers introduced a type of diet that reduced dopamine function in healthy human participants to assess whether it would control the shift between goal-directed action to habitual action.

The participants did not have reduced ability to learn associations between a stimulus and a response. They were also sensitive to outcome devaluation. However, they showed impairments in the slip-of-action test.

Note: the above was shown to occur in women only.

A type of chemical messenger. Dopamine levels spike in certain brain regions in response to a reward. They also sometimes spike in anticipation of a reward.

Once the reward is over, dopamine levels will return to normal. Cocaine stops dopamine from being cleared from the synapse by binding to dopamine transporters, so cocaine can cause a larger than normal response, resulting in greater reinforcement.

Stressful life events, decreased accuracy in responding to training, and cocaine addiction are factors that predict how likely someone is to develop habitual behaviors.

The authors found that cocaine explained 13% of the variance in performance in this study. This means that addiction to cocaine seems to play a significant role in developing habitual behaviors, but that there are also other things that play a greater role.

A method used to reinforce an association with a certain stimulus. Unlike classical conditioning, instrumental learning (otherwise known as operant conditioning) is active and involves a person performing behaviors that are positively or negatively reinforced. Reinforcement is also known as learning.

The two instrumental tasks used in this study were reward and avoidance learning. Participants learned that using a pedal would allow them to avoid being shocked when presented with pictures that they had learned to associate with a shock.

Skin can become a better or worse conductor of energy/electricity when it is presented with stimuli that represent arousal. When something is physiologically arousing (e.g. scary), the electrical conductance of our skin increases because certain sweat glands become more active. Because of this, skin conductivity is an important indicator of attention and memory function.

Neurons that can be activated by stimuli associated with rewards.

A stimulus that is used to trigger a learned response.

For example, let’s say that you like ice cream, and every time you go to your aunt’s house she gives you your favorite ice cream. Now you tend to associate visiting your aunt with getting ice cream. The stimulus is visiting your aunt, and the association is getting ice cream.

A test for habitual behavior. Certain stimuli that were previously associated with a reward are devalued, meaning the reward is removed.

Once the reward is removed, responding to a stimulus no longer makes sense. If people continue to respond, their response is considered habitual.

CUD patients had more difficulty than controls in learning which pictures were no longer associated with a reward. They were also less able to change their responses based on new information, meaning that they continued to respond the same way even in the absence of a reward. Control participants, on the other hand, decreased their response when the reward was removed.

A response that prevents a (usually negative) outcome from occurring.

Skin conductance measures the activity of certain sweat glands, which become more active during the avoidance response (resulting in a higher skin conductance).

It was measured 0.5 to 5 seconds after each stimulus was presented. Conductance allowed the authors to measure how the participants respond to seeing the stimulus before reacting to it and to make sure they had learned to fear the stimuli associated with a shock. This way, they knew that if participants performed poorly in the task, it was not because they did not learn to fear the stimuli.

A test that allows scientists to test for habitual behavior by devaluing certain stimuli that people were trained to associate with a reward. After the stimuli have been devalued, it no longer makes sense to respond to them because there is no longer a reward. If people continue to respond, their behavior is considered habitual.

A guide used to classify and diagnose many different mental disorders, such as drug use and dependence.

For substance abuse, some of the considerations are failure to perform normal tasks and functions, legal problems, and physical hazards. For drug dependence, it assesses the need for higher doses, the amount of effort and risk to get the drug, and the persistence of use. All of these must be recurrent problems to be classified as a disorder.

Previous work has shown how chronic stress and cocaine can affect normal behavior in rats by making them less sensitive to outcome devaluation and more likely to develop stimulus-driven behaviors from previously goal-directed behaviors.

A behavior that has become associated with a change in the environment over time. Stimulus-driven habits will be performed almost automatically.

Over time, people who regularly use drugs may start to use them habitually. This means that they no longer use drugs because it makes them feel good, but because that's just what they do.

When a habit is compulsive, it is performed even without regard to its negative consequences.

In one study, rats that had learned to do a specific task in order to get cocaine tended to continue doing the task even when cocaine consumption was paired with a negative event (here, injection with lithium chloride, which makes rats feel sick).

Behavior that has a specific outcome in mind, like feelings of enjoyment or avoiding discomfort.

Aberrant learning processes refer to the transition of drug seeking and taking from a goal-directed behavior to a habitual behavior. This transition can be artificially enhanced by cocaine. Over time, the habitual brain system can play a larger role and leave someone vulnerable to compulsive behaviors (seeking and taking drugs without a goal, like desiring a rush or avoiding feelings of discomfort).

Reckless, foolish, or inappropriate. Here, the author refers to behaviors that can have consequences on health, social life (e.g. personal relationships), employment, housing, and more.

The National Institute on Drug Abuse provides information about treatments for cocaine addiction, including the length of treatment and what makes a treatment successful. It also highlights how drug addiction compares to other chronic illnesses.

Read more at the National Institute on Drug Abuse:

https://www.drugabuse.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/frequently-asked-questions/how-effective-drug-addiction-treatment

Salamone and Correa review evidence for the fact that motivation is the main process for reinforcement. They also discuss how low/moderate doses of a dopamine receptor-blocking drug can block some actions but leave other behavior intact.

This study and others suggest that the behavior in drug addiction can’t be explained simply by dopamine activation of reward responses, but is instead a complex subject.

Schoenbaum and Setlow were interested in what drives continued drug use even if when it has negative consequences.

The authors use reinforced devaluation to test whether drug exposed rats respond persistently after devaluation of a food reward.

Dias-Ferreira et al. used rats as a model to study how chronic stress affects decision-making processes. His group was able to show that stress affects this process by causing changes in the physiology of neurons and brain regions associated with these functions.

Corbit et al. were interested in how control can be reestablished after drug abuse.

The authors assessed whether chronic drug use shifts behavior from a goal-oriented process to a habit learning process, and studied the physiological implications of those changes. In addition, they tested whether N-acetylcystine, a treatment previously shown to prevent relapse into cocaine use, could prevent the rapid formation of habits after drug exposure.

Balleine and O’Doherty review what is known about the decision-making process, looking at the relationship between action and outcome (goal-directed behavior) and the stimulus-response association (habitual behavior).

The authors discuss the similarity between humans and rats in the decision-making process, showing that for both organisms the cortex and striatum areas are involved in goal-directed and habitual actions.

It is this similarity that suggests that cooperation or competition between habitual and goal-directed actions mediates the integration of new information (learning).

This article discusses whether a given behavior is an acquired habit to a stimulus or is a choice made due to an association between action and outcome (i.e., goal-oriented).

For this study, the author used a food-reward experiment in rats and assessed their actions when the reward was gradually decreased. Extended training affected the relationship between stimulus and outcome, and limited training resulted in the rats being more likely to react to reward devaluation.

This review by Everitt and Robbins discusses what is known about the transition from initial drug use to a habit.

The article takes a physiological perspective by looking at the role of different areas of the brain in this transition, such as the amygdala and hippocampus.

A chronic disorder characterized by uncontrollable repetition of behaviors and uncontrollable thoughts.

The likelihood of an individual developing a disease or being injured.

Characteristics, symptoms, or behaviors that are shared across different psychological diseases and that may represent similar underlying causes.

The authors use the term to highlight the similarities between CUD and obsessive-compulsive disorder. The connection may represent a similar underlying mechanism and suggests that CUD patients could be more prone to developing compulsive habits.

Two diseases or medical conditions that occur simultaneously in a patient.

Opiate-dependent patients might have impaired avoidance habits.

Opiates are highly addictive drugs that are often used to treat chronic pain. Patients that are prescribed these medications sometimes experience withdrawal symptoms within hours of their last dose.

Some patients will misuse the drug in trying to cope with chronic pain as well to avoid their withdrawal symptoms. In one study, the authors inferred that patients' avoidance response to punishment or aversive treatment would be higher compared to cocaine users, since these behaviors can make someone more susceptible to opiate addiction in the first place.

To learn more about withdrawal management: https://www.ncbi.nlm.nih.gov/books/NBK310652/

Symptoms like anxiety, irritability, depression, and drug cravings that often occur when an addicted person stops using a drug.

Alcohol use in humans alters brain regions involved in goal-directed behaviors, which can lead to an increase in habit-learning behaviors in these patients.

There is a shift from goal-directed actions towards habitual actions in patients with alcohol dependency. It is possible that alcohol-seeking behavior alters the capacity of individuals to shift between these two types of behaviors.

Participants with Parkinson's disease have deficits in learning from trial and error. They also had difficulty learning from a positive outcome. Dopamine administration allowed participants with Parkinson's to learn from both positive and negative outcomes, suggesting that their impairment resulted from depletion of dopamine in the basal ganglia.

A learned association between a stimulus and negative outcomes, in this case represented by pictures associated with an electric shock.

Learn more about fear conditioning (animal study): https://www.youtube.com/watch?v=ozkpK-nhz04

Reinforcement that allows the association of a symbol with a positive outcome, in this case money. After trials, the objective was to teach participants to respond to the animal pictures associated with a reward.

Values associated with stimuli. It allows individuals to perceive or react positively or negatively to a presented stimulus.

Impulsivity in rats’ behavior is what leads to compulsive cocaine-seeking behavior despite negative outcomes.

The flow of dopamine within the striatum.

The striatum is a part of the brain that is involved in the motor and reward system. This part of the brain receives dopamine to mediate motor and reward behaviors.

Dopaminergic neurotransmission is the regulation of the release of dopamine from the terminal end of a neuron (axon), the clearance of it (mediated by transporters), diffusion, and its metabolism.

Due to impairment in brain function, CUD patients are unable to control impulses and avoid negative outcomes.

Since CUD patients have an impairment in the brain regions that control responses to stimuli associated with both reward or punishment, it is likely that these impairments are what is giving rise to the high impulsive behaviors observed in CUD patients as compared to the control group.

This task establishes an association between a neutral stimulus and a negative outcome with the hope that the repetitive task will teach participants to avoid the stimulus.

In this study, the negative stimulus was an electric shock over four stages of learning.

The determination of the correlation coefficient.

In this study, the authors used both Pearson (r) and Spearman (rho) correlations. Pearson correlation is used when there is an assumed normal distribution (distribution that shows symmetry around the mean), while Spearman is used when it is assumed the distribution will not be normal.

Learn more about coefficient determination:

http://blog.uwgb.edu/bansalg/statistics-data-analytics/linear-regression/what-does-coefficient-of-determination-explain-in-terms-of-variation/

A drug that competes with dopamine for binding to the dopamine receptor. When the drug binds to the dopamine receptor, dopamine can no longer bind to it, preventing the effect of dopamine signaling.

Animals under dopamine depletion or blockade respond to fear conditioning by urinating, but they fail to respond by avoiding electric shock. These animals show a deficit in initiating a response, but they do not show deficits in their ability to learn associations.

The eight blocks (96 trials) where participants were tested and learned from the feedback that they received after their response to the presentation of the pictures.

A urine screen is performed to rule out medical conditions and/or drug use. In this case, the authors used it to determine if the volunteers were appropriate for their study and to see if they tested positive for drug use for the different types of drugs involved.

A variable that is predicted to interact with the variable being tested in a study (and that might affect the outcome of the study).

The continued use of the drug (cocaine) regardless of health and social consequences.

A test that makes it easier to analyze data that aren’t normally distributed. The authors performed this analysis to reduce skewness (effects due to asymmetry in a probability distribution) and stabilize variance from the questionnaires and demographic responses.

To learn more about transformation: http://fmwww.bc.edu/repec/bocode/t/transint.html

Rats who were given cocaine respond normally to tasks that are meant to completely remove an association with a stimulus. However, they did not respond normally to tasks that were meant to devalue an association with a stimulus, suggesting they were unable to use new information about consequences to guide their behavior.

Why is it that some people use drugs without becoming addicted, while others will continue to abuse a substance despite consequences such as jail time and health problems?

Read more at the Association for Psychological Science:

https://www.psychologicalscience.org/publications/observer/obsonline/how-a-habit-becomes-an-addiction.html

This article covers how constant cocaine use affects areas of the brain such as the amygdala, which is associated with the stimulus and response/feeling after drug consumption. Cocaine exposure also alters the prefrontal cortex, which help individuals to select or take an action base on negatively- or positively-associated outcomes. It also discusses N-acetylcysteine, a treatment that was not entirely successful in human trials, but was helpful to individuals in the decision to refrain from drug use.

Read more at Neuroscience News and Research:

https://www.technologynetworks.com/neuroscience/news/cocaine-addiction-scientists-discover-back-door-brain-283940