L1 - craving, neural basis Flashcards

Question

What is the central question the brain disease model poses?

Answer 1

Why do individuals with a drug addiction continue to use drugs or alcohol despite being aware of the disastrous consequences?

Answer 2

Addiction is a chronic, relapsing brain disease with neurobiological and genetic basis - Chronic disease similar to other chronic diseases such as Type II diabetes, cancer and cardiovascular disease - The name is misleading - it's not negating importance of other factors - sees it as a complex disease with genetic/neurobiological; psychological; environmental/social contributions but ultimately there is emphasis on the neural basis (picture 1)

Answer 3

- Associated with changes in the brain - drugs have effects on the brain - decreased brain metabolism and structural differences compared to healthy controls

Answer 4

1. Hyperactive reward system, sensitized to drug reward: craving and habits 2. Cognitive dysfunction According to the model: Addiction is a chronic, relapsing brain disease, that is **characterised by compulsive drug seeking and use, despite harmful consequences.**

Answer 5

Addiction is a **disease that deserves treatment** - Calling it a disease allows to put the guilt [and stigma] aside so that we can do the work that we need to do (*anonymous recovering alcoholic*)

Answer 6

- Shifts the responsibility away from the persom and might undermine the person's ability to change the addictive, maladaptive behaviour Examples of critics: - *Most people beat addiction by working really hard at it. If only we could say the same about medical diseases!* (Marc Lewing, 2012: wy is addiction not a brain disease) - In Addiction: a Disorder of Choice (2009), Gene Heyman describes addictive behavior as both voluntary and self-destructive *People take heroin out of choice, ultimately, and so can stop out of choice.* *Addicts are not blameless victims of some terrible illness they have no control over* (Theodore Dalrymple, author of ‘romancing opiates’)

Answer 7

- I. Leshner (previous director of the National Institute on Drug Abuse - NIDA) argues drug addiction is a chronic, relapsing brain disease resulting from the prolonged effects of drugs on the brain - Takes into consideration the behavioural and social-context aspects of addiction but puts emphasis on the fundamental role of neurobiological changes - Therefore, effective treatment must include biological, behavioural, and social-context components - Recognizing addiction as a brain disorder characterized by compulsive drug seeking and use can positively influence public health and social policy strategies, ultimately reducing the associated health and social costs

Answer 8

- A wide gap exists between scientific facts and public perceptions - There have been lot of scientific advancements - e.g. significant differences between the brainss of addicted and non-addicted individuals - Through such advancements, science has established that drug abuse and addiction are as much health problems as they are social problems - Despite these advancements, many people view drug abuse and addiction primarily as social problems requiring only social solutions, particularly through the criminal justice system

Answer 9

1. The normal delay in translating any scientific knowledge into practical applications and policy 2. The tremendous **stigma** associated with being a drug user or an addict ↪ public: addicts = victims of their social circumstances or weak and bad individuals lacking the will to lead moral lives and control their behaviour ↪ science: addiction is a chronic, relapsing illness characterized by compulsive drug seeking and use 3. Ingrained ideologies held by some professionals in drug abuse prevention and addiction treatment ↪ e.g. many drug abuse workers are former users who have had positive experiences with a particular treatment method and may strongly advocate for that single approach, even when faced with contradictory scientific evidence

Answer 10

- It affects both individual and public health - It has well-known and severe negative health consequences, both mental and physical - It has significant public health implications since drug use, directly or indirectly, is a platform for violence and the transmission of serious infectious diseases such as AIDS, hepatitis, and tuberculosis - Hence, a committed public health approach, including extensive education and prevention efforts, treatment, and research, is essential

Answer 11

The presence of dramatic physical withdrawal symptoms upon cessation of the drug - the more severe withdrawal symptoms = more serious or dangerous drug

Answer 12

- Whether a drug causes compulsive drug seeking and use, even in the face of negative health and social consequences - These behaviours are the essence of addiction, are most significant to the patient, and should be the focus of treatment efforts - These elements are also responsible for the substantial health and social problems associated with drug addiction

Answer 13

1. Despite the differing mechanisms of action, all drugs have common effects on the mesolimbic reward system (NA) 2. Prolonged drug use causes pervasive and long-lasting changes in brain function at molecular, cellular, structural, and functional levels ↪ The addicted brain is distinctly different from the non-addicted brain, with alterations in metabolic activity, receptor availability, gene expression, and responsiveness to environmental cues ↪ This link to changes in brain structure and function is what fundamentally defines addiction as a brain disease ↪ A metaphorical switch in the brain seems to be triggered by prolonged drug use, moving an individual from voluntary drug use to a state of addiction characterized by compulsive drug seeking and use

Answer 14

- Major goal of treatment must be to either reverse or compensate for these changes in the brain, which can be achieved through medications or behavioural treatments - Research into the biology underlying this "switch" is crucial for developing more effective treatments, particularly anti-addiction medications

Answer 15

- The social contexts in which addiction develops and is expressed are critically important - The example of returning Vietnam War veterans addicted to heroin illustrates this point - Their addictions were relatively easily treated upon their return to the United States because they were removed from the environmental cues associated with their drug use in Vietnam - This highlights the significant role of **conditioned environmental cues** in causing persistent cravings and relapses - Understanding addiction as a psycho-biological illness with critical biological, behavioural, and social-context components implies that treatment strategies must also include these elements

Answer 16

- Addiction is typically a chronic, relapsing disorder, not an acute illness - Total abstinence after a single treatment episode is rare, with relapses being more common - Therefore, addiction should be approached like other chronic illnesses such as diabetes, where management of the illness, rather than a complete cure, is the reasonable expectation and standard for treatment success - This should influence how treatment effectiveness and outcomes are evaluated

Answer 17

- If criminals are known to be drug-addicted, simply incarcerating them without treatment is counterproductive - Untreated addicts have high rates of recidivism (tendency to reoffend) for both crime and drug use, which can be dramatically reduced with treatment during imprisonment

Answer 18

- Looking at addiction as a brain disease affects how society approaches and deals with addicted individuals - Even if initial drug use is voluntary, an addict's brain is different and needs to be treated accordingly - Just as societal approaches to mental illnesses like schizophrenia have evolved from imprisonment to medical treatment, a similar shift in perspective is needed for addiction - Treatment is necessary to address the altered brain function and the associated behavioural and social functioning aspects of the illness - The lack of success of historical policy strategies solely focused on social or criminal justice aspects is partly explained by the fact that they miss the crucial element of the brain's role in addiction

Answer 19

**C. The contribution of psychological and social factors to the development of addiction is negligible.**

Answer 20

- **Anticipation**: Fatima (43 years, GD) described anticipation in the craving experience as being about to approach something good: “It becomes like a heat, … like happiness, when you feel: ‘damn, it is close to things going very well’.” - **Sensory experience** (e.g., visual/taste): For participants with AUD, it could involve the taste sensory, “taste of wine” (Henry, 48 years, AUD) and being absorbed by a “sweet feeling” and visual description of a particular brand of alcohol. - **Me, there and then imagery**: Fatima (43 years, GD) described an imagery: “it is the image of me on the sofa, with a glass of wine and this happy smile.

Answer 21

- Strong craving is common across substance use disorders, and is thought to play an important role in relapse - Cravings would dissappear by themselves after some time but that is very difficult to realize when you're in the middle of it - Craving can be accompanied by repetitive, intrusive thoughts (“I want/need a drink to releave this craving”) that pose further risk to recovery

Answer 22

Several self-report measures have been developed to measure craving: - E.g., the Questionnaire on Smoking Urges; and the Obsessive-Compulsive Drinking Scale: ↪ If you don’t drink, how much of your time is taken up by thoughts, ideas, impulses or images related to drinking? ↪ If you don’t drink, how much effort does it take to counter or ignore these thoughts or to raise your thoughts elsewhere when they come to mind?

Answer 23

Substances of abuse increase extracellular dopamine much more than natural reinforcers - Typically dopamine increases in response to natural rewards such as food - important for survival - When substances of abuse (e.g. cocaine) is taken, dopamine increases are exaggerated and communication is altered - picture 2

Answer 24

- In microdialysis study - probe is inserted into the brain to measure neurotransmitters, in this case dopamine - The rat is presented with piece of food and we can see surge of dopamine release, showing that rewards lead to increased release of dopamine levels in the nucleus accumbens - Might represent the anticipation of reward and the craving

Answer 25

- The process is the same via the microdialysis studies but instead of food, the rat is offered a substance of abuse - While natural reinforces lead to a modest increase in dopamine release in the **nucleus accumbens**, substances of abuse strongly increase it

Answer 26

- Drug-associated cues also evoke a strong dopamine response - Drugs hijack the brain's natural reward system - Exposure to drug and drug-associated cues → dopamine release in nucleus accumbens → craving

Answer 27

The mesolimbic pathway which involves the striatum which is a small group of **subcortical** structures in the basal ganglia; it involves: 1. Caudate 2. Putamen 3. Nucleaus Accumbens (often referred to as ventral striatum)

Answer 28

Dopamine neurons in the **ventral tegmental area** (VTA) project to the nucleus accumbens

Answer 29

- PET studies show lower density of dopamine D2 receptors in the striatum of addicted individuals, relative to controls - Consequence or predictor of substance abuse?

Answer 30

- The reduces density of D2 receptors is a consequence of substance abuse - these patterns result from homeostasic-compensatory brain changes after chronic drug use in order to lower dopamine (DA) transmission: Balance is established through down-regulation of D2 receptors - Increased dopamine activity due to changes → decrease of dopamine D2 receptors - D2 receptor down-regulation may also underlie decreased reward sensitivity to natural rewards in addiction (anhedonia, dysphoria, natural rewards too weak), and tolerance to the reinforcing effects of the drug

Answer 31

- With animal research we can study causal relationships - To this end, PET scanning was conducted at different time points in monkeys using cocaine to measure D2 receptor density - Results in picture 3 - Chronic cocaine use can indeed cause D2 recpetion downregulation - Furthermore, D2 receptor density can recover (increase) following a period of abstinence

Answer 32

- low dopamine D2 receptor availability appears to be more than just a transient consequence of chronic drug use, as direct relatives of drug addicts also show relatively low D2 density - According to the **Reward deficiency syndrome** theory, the number of D2 receptors relates to individual differences in reward sensitivity: less receptors means lower reward sensitivity and higher vulnerability for addiction (natural rewards such as food are not sufficient) - To conclude, there is evidence for both directions

Answer 33

Returning to a particular place or seeing a person associated with drug use - Pavlovian conditioning plays a role

Answer 34

- A change in behavior due to experience with a relationship between a (neutral) conditioned stimulus (CS) and a (motivationally relevant) unconditioned stimulus (US) - After conditioning: the conditioned stimulus elicits the conditioned response - Conditioned response cannot be any behaviour, it's programmed in our evolution how we react to cues that predict rewards - CR: craving, motivational urge, increased approach-behaviour towards that stimulus, mental imagery/expectation of US

Answer 35

- To investigate this, in **cue reactivity fMRI studies**, participants are shown images of alcohol or drugs, as well as neutral images (e.g., nonalcoholic drinks) - To reveal brain activity reflecting cue reactivity to alcohol/drug images, researchers compare the BOLD (blood-oxygenation-level-dependent) signal during exposure to alcohol/drug images with the signal during neutral images - When drug users are exposed to images of drugs/alcohol and associated stimuli in cue reactivity studies, this tends to ‘activate’ quite consistently the nucleus accumbens relative to neutral images - Studies have shown that this correlates with cue-induced self-reported craving

Answer 36

- single cell recordings in monkeys to Pavlovian cues - Extremely thin electrodes were implanted in the animal’s midbrain (comprising the ventral tegmental area (VTA) and substantia nigra (SN)) nearby or inside DA neurons to detect action potentials (phasic dopamine activity) - Pavlovian learning paradigm: Monkeys learned to predict the delivery of fruit juice (US) based on visual icons (CS)

Answer 37

- At the start of CS-US training, after the presentation of the fruit juice (unexpected reward) there is a spike in activity in the VTA and SN - But after the CS-US training, the spike happens at the cue that signals the receiving of the juice - response transfers to reward predictors (picture 4) - Hence, suprising, motivationally significant events (unpredicted USs and CSs) are reflected in phasic dopamine firing

Answer 38

- When the prediction of reward in that situation is not yet completely accurate, this leads to surprise and a reward prediction error occurs - Midbrain dopamine neurons encode this prediction error. This is a signal to cortico-striatal brain circuits that the current reward value does not match the expected value. So it functions as a **teaching signal** ↪ it spikes when something better than expected happens, helping us to learn what predicts good outcomes - Once the Pavlovian CS-US relationship has been learned, the predictive cue (CS) will evoke a dopamine response. Therefore, the DA neurons fire at the (unexpected) presentation of the CS (instead of the fully predicted US) - In normal learning, dopamine signals diminish once predictions are accurate. But drug-induced dopamine doesn't follow this rule - the dopamine surge continues no matter how predictable the drug is

Answer 39

- Picture 5 ↪ Natural reinforcers: moderate training: dopamine spikes at the cue (predicting food), and less at the reward; after extended training: Dopamine spike is only at the cue, not at reward ➜ This is **adaptive learning**: the brain learns that the cue predicts the reward, so dopamine shifts to the cue ↪ unlike natural reinforcers, drugs continue to evoke the dopamine response even if they are already predicted since they cause pharmacological dopamine release and block dopamine reuptake, flooding the brain with dopamine far beyond natural levels = dopamine spikes happen both at the cue and at the drug infusion ↪ Dopamine response to the drug itself doesn't go away, even after lots of learning which leads to **persistent dopamine signals**, reinforcing drug cues more stronly than natural rewards - The **temporal difference (aberrant learning) account** of dopamine function in addiction explains this - over repeated drug use, the repetition of these dopamine signals would continue to reinforce drug-related cues and actions to pathological levels - In comparison to natural reinforcers, cocaine results in differences in phasic dopamine signal in the NA and that has consequences for learning → **aberrant learning**, i.e. drug-related cues get pathologically overvalued

Answer 40

- The mesolimbic dopamine pathway (Ventral Tegmental Area → Nuceus Accumbens) plays a role in craving and is hijacked in addiction, as reflected in multiple ways in which it is affected byacute and chronic drug use (e.g., as reflected in receptor density, extracellular DA levels NAcc, DA neuron activity midbrain, fMRI BOLD signal NAcc) - Some of these have been linked to genetic vulnerabilities to addiction - In any case, there appears to be a vicious cycle, with chronic drug use increasing dopamine levels, leading to dopamine D2 receptor downregulation, which in turn leads to anhedonia and tolerance, thereby contributing to the escalation of drug use

Answer 41

B. CS = television, CR = salivating

Answer 42

A. At the start of Pavlovian training

Answer 43

- Soldiers were taking heroin regularly in a very specific context: combat stress, jungle environment, other users, routines of war - In that setting, tons of cues (visual, emotional, sensory) became linked to the drug - So their brains were firing dopamine in response to those cues, reinforcing heroin use in that setting - Those Vietnam-specific cues were gone — no jungle, no war zone, no wartime peers - Therefore, the brain wasn’t getting the same dopamine cue-triggered drive to seek the drug - Without those predictive cues, there was no strong craving → many didn’t relapse

Answer 44

- Proposed by Kent Berridge & Terry Robinson - A pathological motivation for drugs (together with impaired cognitive control, possibly due to prefrontal cortex dysfunction - not the main thing) is the core problem in addiction - According to I-S theory, the incentive salience of drug-associated stimuli increases in substance abuse

Answer 45

- Psychological processes mediated by brain systems that direct behaviour towards natural rewards, such as food, water, sex - Hightens perception and focuses attention toward the particular sights, sounds, and smells associted with these rewards in a way that normally promotes well-being and survival - The brain's way of saying, “This is important—pay attention to it and seek it out''

Answer 46

It's expressed behaviorally most prominently in the following 3 ways: 1. Drug-associated stimuli elicit attention and approach towards them (they become ‘wanted’), acting as ‘motivational magnets’ 2. Drug-associated stimuli become reinforcers in their own right 3. Drug-associated stimuli (and drugs) can induce relapse Furthermore, incentive sensitization is expressed behaviorally in an increasing willingness to work for the drug

Answer 47

- Sensitization is an increase in a drug effect after repeated exposure - Incentive sensitization specifically refers to neurobiological changes in brain mesolimbic dopamine systems that mediates incentive salience ("wanting") - increased ability of drugs to elevate dopamine neurotransmission in NA and other stuctures - Psychologically, incentive sensitization manifests as increased ''wanting'' for specific rewards, particularly when encountering related cues, and is expressed in seeking behaviour and sometimes subjective ratings - This sensitization of brain systems mediates the incentive motivation for drug rewards and cues, leading to **pathological drug motivation**

Answer 48

- This pathological motivation is due to the effect of repeated substance use on the mesolimbic dopamine system (including the nucleus accumbens - increased dopamine transition in NA), that plays a role in motivational processes and craving - Specifically, this system becomes sensitized (hyperreactive) to the incentive motivational effects of drugs and drug-associated cues, a process called **neural sensitization** - This sensitization leads to attentional bias towards drug-related stimuli and pathological motivation (compulsive ''wanting'') for drugs

Answer 49

- Neural sensitization explains that repeated drug use leads to increased “**wanting**”: extreme craving that does not have to be experienced consciously, and that is triggered especially by drug associated cues - This intensified "wanting" is focused on drugs due to their potent activation of the mesolimbic brain system and the enduring sensitization of that system - This increased "wanting" is not matched by an increase in "liking" (hedonic experience is not dopamine-dependent) for the drugs, as these are mediated by separate brain mechanisms - Only "wanting" systems sensitize, leading to intense "wanting" regardless of whether the drug is still liked - Sensitized "wanting" can be triggered by drug-associated cues or mental representations, especially in specific contexts like previous drug use or stress - Addiction is driven by “wanting”, not liking - chasing the first high

Answer 50

1. **Individual susceptibility** to sensitization varies due to genetic, hormonal, gender, previous drug experiences, and prior stress 2. Drug itself - different drugs induce sensitization to varying degrees and sensitization to one drug can often cross to others 3. Higher doses and repeated but intermittent use, especially with periods of abstinence, increase sensitization 4. The speed at which drugs reach the brain and extended access leading to increased intake

Answer 51

- Once sensitization occurs, even small amounts of the drug can enhance the influence of cues due to the dopamine system being hyperactive to drugs and drug-related cues - This can create unusally strong ''wanting'' for drugs, with a sensitizd brain responding to reward cues as if it has been exposed to amphetamine (stimulant), even without the drug present - Addicts, on encountering the right drug cue, would intensely "want" a cued reward because of excessive incentive salience even if they expect that they won't like it - !! Sensitization can persist for years after drug use cessation

Answer 52

- Addiction starts with pleasant drug effects, followed by continued use to avoid unpleasant withdrawal symptoms upon cessation - Compulsive drug taking is seen as a way to avoid these withdrawal "lows" - There are many hedonic/withdrawal theories, under different names, but they share the basic logic that drugs are initially taken for pleasure and later to escape withdrawal

Answer 53

1. Drug withdrawal = less powerful in motivating drug-taking as compared to the positive incentive processes caused by drugs and their cues ↪ Animal studies show that a small "priming" injection of the drug is far more effective at reinstating drug-seeking behaviour than inducing withdrawal with naltrexone ↪ Withdrawal appears relatively ineffective at directly motivating drug taking without prior learning that the drug can alleviate withdrawal 2. While withdrawal symptoms peak within a few days, susceptibility to relapse can increase for weeks or months ↪ Some addicts' reports support this as they describe that craving is distinct from withdrawal sickness 4. Explaining relapse long after withdrawal symptoms have subsided ↪ Conditioned withdrawal effects elicited by drug cues have been proposed, but many addicts don't report experiencing them, and when they do, it isn't always the primary reason for relapse ## Footnote Nonetheless, withdrawal states may contribute to drug taking while they last

Answer 54

- Evidence suggest that NA and dopamine-related circuitry are involved in reward learning, leading to the idea that drugs might alter learning processes in addicts, causing the transition to addiction - Cues predicting rewards can strongly activate NA circuitry, sometimes more than the reward itself - Repeated drug exposure facilitates certain types of learning and triggers similar neuroadaptations in reward-related neurons as seen in learning - Hence, some reseachers hypothesized that addiction results from the ability of drugs to promote aberrant learning

Answer 55

- Addiction arises from drugs facilitating the learning of strong automatic stimulus-response (S-R) habits - When drugs strengthen automatic S-R habits (like using a drug when seeing a certain cue), these habits by their very nature tend to become compulsive - meaning people feel driven to repeat the behavior even if they consciously don’t want to or know it’s harmful

Answer 56

- They argue that automatic habits aren't necessarily compulsive simply by being well-learned - Habits tend to occur when one's attention wanders, not when consciously trying to do something else (e.g. putting on pyjamas instead of a suit when entering one's bedroom) - yes habits are automatic but if we were truly focused on our goal, we would probably be able to overirse the habit - Repetition alone doesn't make a habit compulsive, as seen in non-compulsive repetitive actions like tying shoes or brushing teeth - Compulsivity requires a motivational component, such as incentive salience ↪ for a habit to become compulsive, your brain has to attach some kind of urgency or desire to it (like the craving associated with drug use) ↪ so it’s not just repetition or automaticity - it’s that the brain now sees the behavior as motivated and necessary - This is similar to the distinction between automaticity and compulsiveness (powerful urge that feels hard to resist) in OCD rituals

Answer 57

- Addictive behaviour also displays targeted flexibility in drug-seeking, which cannot be explained by inflexible S-R habits - Addicts are resourceful and will perform new actions to obtain drugs, unlike S-R automatons who would repeat ineffective habitual actions

Answer 58

- They suggest that learning is only one part of the reward process and not the primary contributor to the pathological pursuit of drugs in addicts - The core idea of incentive-sensitization theory is that repeated drug exposure can persistently change brain cells and circuits in susceptible individuals in a way not reducible to learning - However, they do agree that S-R associations are responsible for the automatized habits in drug consumption once the drugs have been obtained and that drug use can facilitate the development of these habits ↪ this possibly involves the dorsal striatum

Answer 59

- Learning is important as it specifies the object of desire (the drug) through associations gained from past experiences and modulates the expression of neural sensitization in specific contexts (and not in others) - However, learning alone is insufficient for pathological drug motivation, which arises from sensitized, nonassociative adaptations in brain circuits mediating incentive motivation - Contextual control, shaped by learning, explains why "wanting" is strongest in drug-associated environments - Additional evidence: Incentive sensitization can sometimes generalize beyond drug-related targets to other rewards like food, sex, and gambling, indicating a difference from learned focus ↪ This is seen in "dopamine dysregulation syndrome" in some patients treated with dopaminergic medications leading them to not only compulsive drug use but also to gambling, food bingeing and hypersexuality

Answer 60

- The evidence is unclear and speculative - Overactivation of dopamine circuits may underlie excessive "wanting" in sex, eating, and gambling, but the clearest evidence is for drug use - It's unclear whether sensitization-type states can emerge without drug or medication use, although repeated intense stress is a possibility - It's plausible that sensitization-like processes contribute to pathological motivation in other addictions, but currently, no direct evidence exists for spontaneous occurrence in the brains of affected individuals - The closest cases might be suggestions that some obese binge eaters have genetic predispositions toward excessive mesolimbic activation

Answer 61

- Damage or dysfunction in cortical mechanisms underlying cognitive choice and decision-making - Studies show changes in executive functions in both addicts and drug-taking animals - Impaired executive control = important in making poor choices about drugs, especially when combined with the pathological incentive motivation from sensitization

Answer 62

- Incentive salience is most evident in cue-triggered "wanting" and motivational magnet effects that strongly attract individuals to reward stimuli - "Wanting" can occur without conscious awareness of the reward - it has causes and targets but not explicit goals (but it can influence cognitive desires) - Cognitive wanting involves a conscious desire for a specific reward with explicit expectations of future outcomes - When the two align, ''wanting'' adds visceral (gut feeling) force to mental desires - But if they dissociate, ''wanting'' leads to irrational and even unconscious seeking behaviours - Another way to distinguish them: utility

Answer 63

1. Decision utility: what we actually decide to do, manifest in choice and pursuit 2. Predicited utility: the expectation of how much a future reward will be liked

Answer 64

- In cognitive wanting, decision utility is closely linked to predicted utility - Incentive salience "wanting" is a pure form of decision utility - "wants" are closely tied to percepts of rewards and associated cues, triggering a motivational burst upon encountering them ↪ it doesn't require clear cognition or conscious feeling, possibly because it is mediated mainly by subcortical brain mechanisms, while cognitive desires rely more on higher cortex - Incentive salience may have evolved to facilitate pursuit of innate incentives = goal-directedness - It's is crucial for filling conscious desires with motivational power, making them compelling, even if its effects are often implicit - it may be a key component of intense and visceral desires, particularly in pathological addictions and compulsions

Answer 65

1. Incentive salience gives a **“motivational magnet”** property to stimuli it is attributed to and makes those stimuli attractive and elicit approach toward them 2. stimuli attributed with incentive salience are “wanted”, leading people/animals to work to get them ↪ even support the learning of new actions to get them (act as conditioned reinforcers) 3. Incentive salience also triggers momentary bursts of intense motivation to obtain a cued reward, often manifest as a “surge” in the instrumental action required to obtain the reward

Answer 66

They use the idea of the two types of wanting to explain why they disagree - A person can *cognitively want* to stay clean (a stable, rational goal), yet still feel a sudden, intense urge to use drugs when exposed to certain cues (''wanting'') - this urge comes from the sensitized incentive salience, making drug-associated cues extremely tempting and difficult to control - Hence, this kind of "wanting" feels compulsive because it can go against a person’s main goal (like staying sober) and still push them toward drug use - Even though people can use self-control to resist these urges, just one slip-up in the right context (like seeing a drug-related cue) can be powerful

Answer 67

Animal studies: blocking dopamine stops the cue-triggered urges ("wanting") but doesn't affect the more thoughtful, goal-based motivations - Also, these urges are brief - they spike when a cue appears, then fade, even if dopamine levels stay high - This suggests that the urge is not just about brain chemistry alone, but also about the interaction between brain systems and external cues

Answer 68

- The incentive-sensitization theory posits that addiction results from drug-induced changes in brain circuits, especially in the mesolimbic system - This theory suggests that addiction stems from abnormal incentive motivation due to sensitization of neural pathways that attribute salience to specific stimuli - Sensitized "wanting," driven by drug cues, persists independently of withdrawal symptoms or cognitive desires and is distinct from the pleasure of drug "liking'' - This can lead to compulsive drug-seeking behavior that becomes irrational and destructive

Answer 69

1. CSs become motivational magnets 2. CSs become reinforcers in their own right 3. CS (and drug) exposure lead to relapse (reinstatement) 4. Willingness/motivation to work for the drug increases We will now look at experimental models of these features

Answer 70

- Through their association with past substance use, locations, situations, people and other stimuli may become “motivational magnets” that draw the user to them, thereby increasing the likelihood of more substance use - This has been studied with the **conditioned place preference paradigm**

Answer 71

- The animal is given access to two chambers where in one it receives a drug (ethanol) and it can decide into which chamber it wants to go and spend time in - The chamber with the drug becomes associated with the drug and it becomes the preferred place for the animal throughout the training - Picture 6

Answer 72

- It's done the same way but with alcohol and can be done in real life or in virtual enviornment (Picture 7) - People spend more time in the room with alcohol; controls spend equal time in both rooms

Answer 73

Through **conditioned reinforcement** which occurs when a stimulus (CS) has acquired the capacity to reinforce behaviors due to its learned association with a (drug) US

Answer 74

- In the first phase, pavlovian conditioning is done: light (CS) → drug (US) - In the second (instrumental) phase, the rat has access to two levers and when one is pushed the light comes on and when the other is pushed, nothing happens - Result: Rats will perform R1 more vigorously than R2, i.e. they seek reinforcement - Furthermore, conditioned reinforcement is potentiated by stimulating dopamine release in the nucleus accumbens

Answer 75

- Through **conditioned reinstatement** which is the ability of drug-associated cues (CS) to powerfully reinstate a previously extinguished instrumental response - For example, after a period of abstinence in a treatment center, return to the original drug-associated context may trigger relapse to the same level of drug seeking as before - NOTE: Even increases in drug seeking have been observed in animals after a period of extinction…. Indeed, craving may increase during extinction - this is referred to as “incubation of “craving”

Answer 76

1. Acquisition: Lever press response → Light (CS = drug-associated cue) + drug 2. Extinction: Lever press response → nothing; so after some time, it will stop pressing the lever 3. Reinstatement test (in extinction): present the light (CS) again → lever press response = **conditioned reinstatement effect** (picture 8)

Answer 77

- Computer task of seeing pictures of a substance (e.g. alcohol or cigarettes) and chocolate or other cue - Instrumental training: R1 → cigarettes; R2 → chocolate - Choice reinstatement test: R1 vs R2 - smokers preferentially perform R1

Answer 78

1. Drug reinstatement, e.g. just having one drink (or hit) leads to a full-blown relapse 2. Stress reinstatement, e.g. a stressful episode at work leads to relapse

Answer 79

- Next to increasing the incentive salience of drug CSs, repeated drug use increases the motivation to obtain the drug - This is studied in **progressive ratio experiments** - Here, the instrumental response requirement to obtain a substance gradually increases - The maximum number of responses that the subject makes in order to receive the substance is referred to as the **break point**

Answer 80

- Primary outcome variable: “the break point”, which is the point at which the animal is no longer willing to press harder for the drug - Importantly, rats will work harder to selfadminister a drug (i.e, reach the breakpoint later) when they have been pre-exposed to this drug (picture 9)

Answer 81

C. When people repeatedly take drugs, this leads to an increasingly strong hedonic experience, thereby decreasing motivation for other rewards (e.g., food or social interaction)

Answer 82

B. Progressive ratio paradigm

Answer 83

The dopamine receptor density is not thought to be critical in the incentive-sensitization model. It's thought to reflect the development of tolerance, rather a side effect than a core of addiction

Answer 84

- According to the incentive-sensitization account, chronic drug use leads to neural sensitization of the mesolimbic dopamine pathway and to incentive sensitization - Drug CSs evoke a strong dopamine signal → these stimuli become hyper-salient and trigger aberrantly strong “wanting“ (even though liking decreases) - Incentive sensitization can persist for years after drug use has been quitted (and withdrawal symptoms are gone), and can thus play a role in relapse, sometimes even after many years of abstinence - In fact, some research even suggests that cue-induced recovery of responding continues to increase for weeks-months after abstinence, i.e. ‘incubation of craving’ - Different measurement methods can be used to study incentive sensitization: ↪ Pavlovian conditioned approach ↪ Conditioned reinforcement ↪ Reinstatement (by CSs, drugs, and stress) ↪ Progressive ratio experiments - These have all been related to dopamine transmission in the mesolimbic dopamine pathway - At the same time, this is also a criticism of the incentive-sensitization theory: the concept is very broad and therefore lacks specificity - Nevertheless, it remains one of the most influential theories of addiction

Answer 85

- Name and explain protective and risk factors for substance use [paraphrasing] - Indicate the difference between Pavlovian and instrumental conditioning [paraphrasing] and be able to apply this to a concrete example of behaviour [analyzing] - Explain how structural differences in the dopamine system can contribute to substance abuse [paraphrasing] - Explain the role of incubation of craving in addiction [paraphrasing] - Explain how “prediction error” is encoded by the mesolimbic dopamine pathway, and how it is affected by substances of abuse [analyzing] - Explain how the “incentive sensitization theory” explains relapse in substance abuse [analyzing] - Explain the different roles of liking and "wanting" in substance abuse [analyzing] - Explain how incentive sensitization is measured [paraphrasing and analyzing] - Apply the above-mentioned research methods to a new research question about liking and "wanting" [independent thinking] - Describe the neural basis of liking and "wanting" [paraphrasing] - Evaluate the role of craving in substance abuse and relapse, using arguments on both a behavioral and neuroscientific level [evaluating and independent thinking