HC.1.2 Flashcards

Question

Name some critics of the brain disease model:

Answer 1

1. Addiction is a choice - Addiction is voluntary behaviour - people can choose to stop, like they choose to start 2. Addicts have some control - portraying addicts as powerless victims is misleading - addicts are not completely without control 3. Addiction isn't like a disease - many recover through personal effort, not medical treatment

Answer 2

- Natural reinforcers trigger moderate dopamine activity. - Cocaine blocks dopamine transporters, preventing reuptake and flooding the synapse with dopamine. This leads to a stronger dopamine release and exaggerated reward signals. Reinforcing drug use far more strongly than everyday pleasures. This strong artificial reward increases the brain's learning about the drug and leads to powerful cravings when reminded of it. Evidence: - Microdialysis studies show that rewards lead to increased release of dopamine levels in the nucleus accumbens. Substances lead to more dopamine release than natural reinforcers in the nucleus accumbens. These spikes of dopamine lead to that the brain learn that drugs are more rewarding than natural reinforcers.

Answer 3

Refers to how addictive substances artificially stimulate the brain’s reward circuitry, causing unnaturally high levels of pleasure and reinforcement. - Natural reinforcing behaviors trigger moderate dopamine release in the nucleus accumbens, motivating you to repeat them. - Drugs like cocaine, nicotine, and opioids cause a massive release of dopamine—far more than natural rewards. - They flood the reward system, sending an exaggerated signal that says: "This is way more rewarding than anything else!" - Over time, the brain becomes rewired to prioritize the drug over natural rewards. - The brain starts treating the drug as essential for survival, just like food or water. - This leads to: --- Compulsive drug-seeking behavior --- Loss of interest in other activities --- Craving, especially in response to drug-related cues Repeated drug use changes brain structure and function: - Reward system becomes less sensitive to normal pleasures. - Prefrontal cortex (self-control) becomes less effective. - Cues and triggers cause dopamine spikes even without the drug present. How the hijacking works: - Drugs (e.g., cocaine, heroin, nicotine) cause dopamine release far beyond natural levels. - The brain overlearns that drug = extreme reward. - Cues (e.g., places, people, paraphernalia) become intensely associated with the drug, even more than the drug itself. - Dopamine responses don’t fade like with natural rewards — instead, they stay high or increase with repetition. - The brain starts prioritizing drug-seeking over everything else: food, relationships, goals.

Answer 4

Cues related to drugs (like seeing a needle or a certain place) can evoke dopamine release. Dopamine spikes in response to these cues lead to intense urges to use again.

Answer 5

The mesolimbic pathway is a key part of the brain's reward system and plays a central role in motivation, reinforcement, craving and addiction. The mesolimbic pathway is a dopaminergic (dopamine-based) neural circuit. It connects: 1. the Ventral Tegmental Area (VTA); starts the dopamine signal and 2. the Nucleus Accumbens (NAcc) (part of the ventral striatum); creates pleasure and motivation This pathway is also linked with: - PFC - Amygdala - Hippocampus How it works: Normal reward response: - When you experience a natural reward (like food, social connection, or achievement), the VTA releases dopamine into the nucleus accumbens. - This makes you feel pleasure and motivation, reinforcing that behavior so you’ll do it again. Drug reward: - Drugs of abuse (e.g., cocaine, nicotine, opioids) hijack this system by triggering an unnatural, massive dopamine release. - This surge is far greater than natural rewards, which causes the brain to: --- Overvalue the drug --- Form strong associations with drug-related cues --- Weaken motivation for other non-drug activities Role in craving: - After repeated use, drug cues (places, people, paraphernalia) activate the mesolimbic pathway, especially the nucleus accumbens. - This dopamine release triggers intense craving, even if the person hasn’t taken the drug recently.

Answer 6

PET studies show lower DA (dopamine) D2 receptors in the striatum of addicted individuals. According to the homeostatic account, the brain adapts to the excessive dopamine stimulation caused by chronic drug use by downregulating D2 receptors. (compensatory). Because of this downregulation, natural rewards feel less pleasurable (decreased reward sensitivity). This may explain tolerance and the loss of motivation for normal life goals in addicts.

Answer 7

- PET studies in monkeys (Nader et al., 2006) show that chronic cocaine use over time causes a progressive drop in D2 receptor density. - The longer the exposure, the greater the reduction — establishing a causal relationship. BUT Direct relatives of drug addicts also show relatively low D2 density. This supports the "Reward Deficiency Syndrome" theory: - Some individuals are born with fewer D2 receptors, making them less sensitive to natural rewards. - They may be more likely to seek stronger stimulation (e.g., drugs) to feel pleasure. > less receptors means lower reward sensitivity and higher vulnerability for addiction Conclusion: Low D2 receptor levels can be both a consequence of drug use and a predisposing risk factor.

Answer 8

D2 receptor levels can recover over time with sustained abstinence. PET scans show that after 14 months of abstinence, methamphetamine abusers show partial restoration of dopamine receptor density, approaching levels seen in healthy individuals. Suggests the brain has plasticity, and some damage from drug use is reversible.

Answer 9

When a neutral stimulus becomes associated with a meaningful stimulus and begins to evoke a similar response on its own. Key terms: - US (unconditioned stimulus): naturally causes a response (e.g. food) - UR: (unconditioned response): salivation to food - CS (conditioned stimulus) > initially a neutral stimulus (e.g. bell) - CR (conditioned response): salivation in response to bell after learning

Answer 10

Just like Pavlov’s dogs learned to salivate to the bell, humans can learn to crave drugs/alcohol through cues like brands, bars, smells, or environments. Example: Seeing a beer logo (CS) triggers mental imagery, craving, or even salivation, because it’s been paired with alcohol (US) repeatedly.

Answer 11

1. Cue reactivity studies (fMRI) expose participants to drug-related images vs. neutral ones. The BOLD (blood-oxygenation-level-dependent) signal (brain activity) reveals how the brain reacts more strongly to drug cues in addicted individuals. 2. In monkeys, dopamine neurons in the VTA/SNc were recorded while learning Pavlovian associations (cue → juice). Findings: - Dopamine spikes initially to unexpected rewards - Over time, the spike shifts to the predictive cue (CS)

Answer 12

In general: At its core, reward prediction error is the difference between what you expect to happen and what actually happens when it comes to rewards. - If something better than expected happens → positive RPE - If it’s exactly as expected → no RPE - If it’s worse or doesn’t happen → negative RPE Dopamine neurons in the ventral tegmental area (VTA) fire in response to: - Unexpected rewards (big dopamine spike) - Cues predicting reward (after learning, the spike shifts to the cue) - Missing rewards (dopamine firing decreases) This phasic dopamine activity acts as a teaching signal, guiding the brain in making predictions about what stimuli in the environment are important or valuable. - Dopamine neurons (mostly in the VTA) signal RPEs. - These signals act like a “teaching signal” to update your expectations and help you learn. - Over time, dopamine shifts from the reward itself to cues that predict the reward (e.g., smell of food before eating). At the beginning of CS-US training there is a burst of dopamine to the unexpected reward (so after the US). But at the end of training, there is already a burst of dopamine after the CS. So the response is transferred to reward predictors. This “shift” in dopamine firing reflects a reward prediction error: - If something better than expected happens → dopamine spike - The brain learns from this to anticipate future rewards - Once learning is complete, dopamine fires to the CS, not the US This is how drug cues gain motivational power—they become reward predictors that grab attention and drive craving.

Answer 13

In natural reward learning, dopamine response to the CS first shift and then declines over time The dopamine system learns associations between cues (CS) and rewards (US). - Dopamine neurons fire when there is a reward prediction error: --- If a reward is better than expected → dopamine spike --- If it's as expected → no spike --- If it's worse or missing → dopamine drop - Over time, dopamine responses shift from the reward (US) to the cue (CS). This helps organisms adaptively learn what cues in the environment signal valuable outcomes. In drug learning, the response also shifts to the cue but also remains high when the drug is obtained, and even increases with repetition - Drugs hijack the dopamine system, causing excessive dopamine spikes, not just for the drug but for cues associated with it (bars, bottles, people, paraphernalia, etc.). - The brain overlearns these associations, and dopamine keeps firing to these cues even if the drug is no longer rewarding or is harmful. - The system fails to extinguish or reduce dopamine response over time (unlike with food or natural rewards). 🎯 Key problem: The brain treats drug cues as if they are incredibly valuable and urgent, even when they aren’t anymore. Consequences of aberrant learning: - Craving is triggered by cues: Just seeing a beer logo or a street corner can induce strong urges. - Compulsive drug seeking: Even when drugs are no longer pleasurable, people continue to pursue them. - Relapse: Environmental triggers can reactivate the entire addiction cycle, even after long abstinence. - Distorted decision-making: The brain assigns excessive value to drugs over other important rewards (e.g., family, health, goals).

Answer 14

This theory is proposed by Berridge and Robinson. It focuses on how repeated drug use changes the brain’s reward system and how this leads to pathological motivation ("wanting") for drugs, even if the actual pleasure ("liking") from using them decreases over time. Core ideas: - Addiction is caused by pathological motivation for drugs due to changes in the brain’s reward system (particularly the mesolimbic dopamine system). - This means people may want the drug intensely, even if they don’t like it anymore. - The theory emphasizes the difference between "wanting" (the motivational pull) and "liking" (the actual pleasure from the drug). Behavioural expression of the theory: At the behavioral level, the increased incentive salience of drug cues results in: 1. Drug cues grab attention and trigger approach behavior – they become “motivational magnets”. 2. These cues become reinforcers in themselves, meaning they can trigger motivation and drug-seeking. 3. Cues can induce relapse even after long periods of abstinence. People might even work harder to get drugs over time, showing that their motivational pull increases. Neural basis of the theory: - The mesolimbic dopamine system, including the nucleus accumbens, becomes hypersensitive (or “sensitized”) to drug-related cues. - This sensitization is neural, meaning it is based on long-lasting brain changes that make the system hyperreactive. - These changes increase craving and compulsive drug seeking, even when the person tries to quit. Key insight: With repeated drug use: - “Wanting” increases (due to sensitized dopamine response to cues). - “Liking” decreases (the pleasure becomes less intense over time). - This dissociation is important: addiction is driven by "wanting", not by pleasure. - The person may not even enjoy the drug anymore, but the craving (triggered by cues) is overwhelming and hard to resist. Conclusion: The Incentive-Sensitization Theory explains why people: - Relapse even after long abstinence, - Feel intense cravings out of nowhere, - Keep using drugs even if they no longer feel good. It highlights how drug cues hijack the brain’s motivation system, creating a powerful, persistent drive that leads to compulsive use.

Answer 15

Incentive salience is a psychological and neurobiological concept that refers to the motivational “pull” or attractiveness of a stimulus, especially one associated with a reward. In simple terms, it's what makes something stand out to you as desirable and “wanted”, drawing your attention and prompting you to seek it out—even if you don’t actually enjoy it. Incentive salience = when something becomes “wanted” because the brain has learned to associate it with reward. It’s not the same as liking. You can want something a lot without actually enjoying it. In the brain: - Driven by dopamine activity in the mesolimbic pathway (especially the nucleus accumbens). - It sensitizes over time with repeated drug use. That means drug-associated cues (e.g., a beer logo, syringe, or environment) become extremely potent in triggering craving and drug-seeking. - This effect can occur even when the drug no longer gives pleasure—the person still wants it intensely because the cues have acquired exaggerated motivational power.

Answer 16

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 is studied with the conditioned place preference paradigm: In animals: - Experiment Setup: -- Animals (like rodents) are exposed to two distinct environments: one paired with a drug (e.g., ethanol), the other with a neutral vehicle. -- After repeated pairings, animals are tested without drug present. - Findings: -- Animals spend more time in the drug-paired environment, indicating a preference. - Neurobiology: Dopamine plays a central role, especially in: -- Ventral tegmental area (VTA): involved in reward processing. -- Nucleus accumbens: dopamine increases here correlate with the conditioned preference. In humans: Similar experimental structure but adapted to humans, using either real or virtual environments. - Design: -- Individuals are exposed to two rooms—one paired with alcohol and the other with a placebo. - Results: -- After training, participants prefer the alcohol-paired room. Indicates that humans, like animals, form motivational associations with drug-paired cues. CONCLUSION: The CPP paradigm demonstrates how environmental cues linked to drug use acquire motivational power, leading individuals—both animals and humans—to seek out those cues, a core idea in the incentive sensitization theory of addiction. This process is dopamine-dependent and helps explain why relapse often occurs in environments previously associated with drug use.

Answer 17

Core Concept: - Conditioned reinforcement occurs when a previously neutral stimulus (a conditioned stimulus, or CS) gains the ability to reinforce behavior after being associated with a biologically significant event (an unconditioned stimulus, or US, like a drug). - In the context of drug use, cues like lights, sounds, or environments that have been paired with drug intake can become motivators for behavior even without the drug being present. Experimental Model (Two-Phase Design): 1. Phase 1: Pavlovian Conditioning Light (CS) is repeatedly paired with drug delivery (US). - The animal learns to associate the light with the rewarding effects of the drug. 2. Phase 2: Instrumental Conditioning Now, the animal is given two behavioral options: - Response 1 (R1) results in the presentation of the light (previously paired with the drug). - Response 2 (R2) results in nothing. - Outcome: Rats perform R1 significantly more than R2, indicating that the light has become a conditioned reinforcer—they are now motivated to work just to experience the cue that was once paired with the drug.

Answer 18

how drug-associated stimuli can trigger relapse by reinstating drug-seeking behavior through a model known as the Reinstatement Paradigm. This is a key component of incentive sensitization theory, emphasizing how conditioned cues, drugs themselves, or stress can reactivate addictive behavior after a period of abstinence or extinction. Conditioned reinstatement is when drug-associated cues (CS) can trigger relapse—i.e., bring back a previously extinguished drug-seeking behavior. it is the ability of drug-associated cues (CS) to powerfully reinstate a previously extinguished instrumental response. - Example: A person abstinent in a treatment center may relapse when re-exposed to an environment where they used to take drugs. Study in animals: 1. Acquisition Phase: Animal learns to press a lever to receive a drug paired with a light (CS). 2. Extinction Phase: Drug and light are removed. The lever press no longer gives any reward → behavior diminishes. 3. Reinstatement Test: Only the light cue (CS) is reintroduced (no drug). - Result: Lever pressing resumes, showing reinstatement of drug-seeking. - This effect is evidence that the cue alone can reactivate the motivational drive for drug-seeking. - This cue-triggered relapse can intensify over time, even during abstinence—a process called “incubation of craving.” Study in humans: - Participants are trained to press a button (R1) for cigarettes or (R2) for chocolate. - In reinstatement tests, smokers prefer R1, especially when exposed to cues like alcohol or stressful situations. - Craving ratings (1–5) can help measure the subjective effect of reinstating triggers. Brain mechanisms: These reinstatement forms involve the mesolimbic dopamine pathway, especially: - The ventral tegmental area (VTA) and - The nucleus accumbens. Blocking activity in these areas can prevent reinstatement, confirming their central role in relapse. CONCLUSION: This model shows that drug relapse is not only a matter of willpower, but deeply tied to cue-reactivity and brain reward circuitry. Drug-associated cues, drug priming, and stress can all independently reignite the motivation to seek drugs after extinction—explaining why relapse is so common and difficult to prevent.

Answer 19

Incubation of craving refers to the phenomenon where craving for a drug actually increases over time during a period of abstinence, rather than fading away. Here's what it means in simple terms: - After someone stops using a drug (e.g., enters treatment or goes through detox), you might expect their cravings to gradually decline. - But research—especially from animal models—shows the opposite: --- The longer the abstinence period, the stronger the craving can become when the individual is re-exposed to drug-associated cues. This means that: - Craving "incubates" or builds up silently over time, even without drug use. - Later exposure to cues (like places, people, or objects linked to drug use) can trigger intense urges, often more powerful than right after stopping. Why it matters: - It helps explain delayed relapse, where someone might stay clean for weeks or months, then suddenly relapse when exposed to a cue. - It emphasizes that time alone doesn't "heal" addiction—cues and brain changes still have powerful effects.

Answer 20

1. conditioned reinstatement 2. Drug reinstatement: A small dose or “taste” of the drug (like one drink) causes full relapse. 3. Stress reinstatement: Stressful events (like a bad day) can trigger relapse

Answer 21

explain how chronic drug use increases the motivation to obtain the drug, as studied through the Progressive Ratio (PR) experimental model—a key component of incentive sensitization theory. 🔁 Core Concept: Repeated drug use doesn't just sensitize someone to cues—it amplifies their motivation to work for the drug. In other words, chronic users are willing to expend more effort to get the drug, even as the required cost (effort) increases 🧪 Experimental Model: Progressive Ratio (PR) Self-Administration How it works: 1. Animals (or humans) are trained to perform an action (e.g., lever press or button push) to receive a drug (e.g., ethanol, cocaine). 2. In PR schedules, the number of required responses increases with each drug reward (e.g., 1 press → drug, then 2 presses → drug, then 4, 6, 9...). 3. The point at which the subject stops responding is called the “break point”—a direct measure of how motivated they are to obtain the drug. Break Point Data – Cocaine Study) - Shows a graph where lever presses increase until a peak, then drop. - The “break point” reflects the maximum effort the animal will invest. - Pre-exposed rats (chronic users) show higher break points, meaning they work harder for the drug. - This is linked to dopamine signaling in the nucleus accumbens, a key reward center. Animal vs. Human Data: Shows parallel PR paradigms in: 1. Animals (e.g., alcohol-preferring vs. control rats) 2. Humans (e.g., individuals with Alcohol Use Disorder vs. light drinkers) - Results show that those with a history of higher use have elevated break points, indicating greater drug motivation. - Demonstrates that this mechanism is conserved across species and clinically relevant. 🧠 Why It Matters: - PR experiments quantify the motivational power of a drug. - The increase in break point after repeated exposure supports the idea that drugs sensitize the brain's motivational systems—even if the pleasurable effects stay the same or decline. - This helps explain compulsive drug-seeking seen in addiction, even when drug use is no longer enjoyable.

HC.1.2 Flashcards

(45 cards)