Drug Flashcards

Question

How do dopamine receptor types and pathways explain addictive behavior and why one drug can cause opposite effects?

Answer 1

Key Findings: • Two Types of Dopamine Receptors • D1 receptors → Excitatory, involved in the direct pathway → facilitates actions (“Go”). • D2 receptors → Inhibitory, involved in the indirect pathway → suppresses actions (“No-go”). • Dopamine’s Role in These Pathways • Enhances direct pathway (via D1) → promotes reward-seeking and goal-directed behavior. • Inhibits indirect pathway (via D2) → reduces behavioral inhibition. • Together, this leads to stronger initiation of rewarding actions and less control over stopping them. • In Addiction • With chronic drug use, dopamine signaling becomes dysregulated. • Direct pathway becomes overactive, reinforcing drug-seeking habits. • Indirect pathway becomes weakened, reducing impulse control and the ability to stop. • This imbalance may explain why people persistently engage in drug use despite negative consequences. Key Takeaway: • Dopamine affects two opposing motor/motivation circuits via different receptors. In addiction, overactivation of the “Go” system and underactivation of the “No-go” system helps explain compulsive drug-seeking behavior.

Answer 2

Key Findings: • Yes. A single neurotransmitter (like dopamine) can act on different receptor types, each triggering distinct effects. • For dopamine: • D1 receptors (excitatory) → enhance the direct pathway → promotes action and reward-seeking. • D2 receptors (inhibitory) → affect the indirect pathway → reduces behavioral inhibition. • So, a drug that increases dopamine (like cocaine) can simultaneously: • Increase motivation and reward-driven behavior • Reduce impulse control Key Takeaway: • One drug can produce different—and even opposing—effects by acting on different receptor types in the brain.

Answer 3

Key Findings: • Amphetamine (安非他命) • A potent stimulant that increases dopamine, norepinephrine, and serotonin levels in the brain. • Works by: • Blocking reuptake of these neurotransmitters • Reversing transporters to cause massive neurotransmitter release into the synapse • Used medically for ADHD (e.g., Adderall) and narcolepsy. • Methamphetamine (甲基苯丙胺) • A stronger, more addictive version of amphetamine. • Crosses the blood-brain barrier faster → produces more intense and longer-lasting effects. • Causes extreme euphoria, energy, but also rapid tolerance, dependence, and neurotoxicity. • Chronic use can lead to dopamine system damage, psychosis, and cognitive decline. Key Takeaway: • Amphetamine and methamphetamine are powerful stimulants that boost dopamine and other monoamines. Methamphetamine acts faster and stronger, making it highly addictive and neurotoxic.

Answer 4

Key Findings: • Short-Term Effects: • Increased alertness, energy, euphoria • Reduced appetite • Increased heart rate and blood pressure • Enhanced focus and confidence (often used medically for ADHD) • Long-Term Use: • Tolerance and dependence • Neurotoxicity → especially to dopamine neurons • Psychiatric symptoms: anxiety, paranoia, hallucinations • Cognitive deficits: memory loss, impaired attention • Physical effects: weight loss, dental issues (especially in meth use) Key Takeaway: • Amphetamines provide short-term stimulation and focus but can lead to addiction, brain damage, and mental health issues with long-term use.

Answer 5

Key Findings: • Alcohol (乙醇) is a central nervous system depressant. • Causes relaxation, reduced anxiety, slowed reflexes, and impaired judgment. • High doses can lead to sedation, unconsciousness, or death from respiratory depression. ⸻ • Mechanism 1 – GABA-A Receptor Activation • Alcohol enhances GABA-A receptor activity. • GABA-A is an inhibitory receptor that lets Cl⁻ ions into neurons. • This hyperpolarizes the cell, making it less likely to fire → produces calming and sedative effects. • Mechanism 2 – Dopamine Release • Alcohol indirectly increases dopamine release in the nucleus accumbens (reward center). • Contributes to feelings of pleasure and reinforcement, which support addictive potential. Key Takeaway: • Alcohol depresses brain activity by enhancing GABA-A inhibition and indirectly increasing dopamine in reward pathways, leading to both sedation and reinforcement.

Answer 6

Key Findings: • After one week of abstinence, researchers measured average brain volume change among three groups: • Abstainers (people who stayed off alcohol) • Relapsers (those who returned to heavy drinking) • Light drinkers • Results: • Abstainers showed significant brain volume recovery after just one week. • Relapsers showed little to no recovery, or continued brain volume loss. • Light drinkers remained relatively stable. • Suggests that the brain can begin to heal quickly when drinking stops— but relapse halts or reverses recovery. Key Takeaway: • The brain shows early signs of volume recovery after stopping alcohol, but relapse prevents healing—highlighting how fast alcohol affects brain structure and how important sustained abstinence is.

Answer 7

Key Findings: • Hallucinogens (致幻剂) • Drugs that cause sensory distortions, altered perception, and sometimes profound changes in thought and emotion. • Common effects: visual or auditory hallucinations, time distortion, synesthesia, ego dissolution. • Examples: LSD, psilocybin (magic mushrooms), mescaline. • LSD (Lysergic acid diethylamide) • A potent synthetic hallucinogen. • Primarily acts as a serotonin (5-HT2A) receptor agonist, especially in the visual cortex and default mode network. • Causes intense visual imagery, disrupted sense of self, and emotionally vivid experiences. • Non-addictive, but can lead to tolerance and psychological distress or “bad trips”. Key Takeaway: • Hallucinogens like LSD alter perception and consciousness by acting on serotonin receptors, especially in sensory and integrative brain regions. LSD produces vivid experiences without being physically addictive.

Answer 8

Key Findings: • The slide shows a visual representation (brain “painting”) based on fMRI scans of the brain under LSD. • It highlights increased global connectivity—brain regions that usually operate independently become more interconnected. • This hyper-connectivity helps explain: • Sensory blending (e.g., synesthesia) • Unusual thoughts and visuals • Altered sense of self or ego dissolution • The painting reflects how LSD leads to a less constrained, more chaotic and integrated brain state, unlike the normal resting brain where regions are more segregated. Key Takeaway: • The fMRI-based painting shows that LSD increases cross-talk between brain regions, helping explain its intense perceptual and emotional effects.

Answer 9

Key Findings: • Substance Abuse and Addiction affect millions of people worldwide. • In the U.S. alone, tens of millions struggle with alcohol, tobacco, or drug addiction each year. • Addiction is recognized as a chronic brain disorder, not just a moral failing. • Social Costs include: • Healthcare expenses (treatment, hospitalizations) • Lost productivity (missed work, unemployment) • Crime and legal system burden (drug-related arrests, incarceration) • Family and relationship breakdown • Costs to education and welfare systems • Economic burden in the U.S. is estimated in the hundreds of billions of dollars per year. Key Takeaway: • Substance abuse and addiction affect millions and carry enormous personal, social, and economic costs—impacting public health, families, and society at large.

Answer 10

Key Findings: • Moral Model (道德模型) • Views drug abuse as a personal failure or moral weakness. • Belief: people choose to use drugs and should be punished or shamed. • Often used in stigmatizing attitudes and punitive policies. • Does not account for biological, psychological, or social factors. • Disease Model (疾病模型) • Treats addiction as a chronic medical condition involving brain changes. • Emphasizes genetics, neurobiology, and environmental influences. • Supports treatment, rehabilitation, and long-term support rather than punishment. • Widely accepted by modern neuroscience and psychiatry. • Addiction (成瘾) • A brain disorder marked by compulsive drug seeking and use, despite negative consequences. • Involves dysregulation of reward and control systems (e.g., dopamine pathways). • Can lead to relapse even after long abstinence. Key Takeaway: • The moral model blames the individual, while the disease model explains addiction as a medical issue rooted in brain dysfunction—shaping how society responds to and treats drug abuse.

Answer 11

Key Findings: • Physical Dependence Model (生理依赖模型) • Suggests that people continue drug use to avoid withdrawal symptoms. • Withdrawal = unpleasant physical or emotional symptoms that occur when drug use stops. • Examples: pain, anxiety, nausea, irritability, sweating. • The model sees addiction as a cycle: 1. Drug use 2. Tolerance 3. Withdrawal 4. Continued use to relieve withdrawal • Limitations: • Doesn’t explain relapse after withdrawal ends. • Some drugs (e.g., cocaine) have mild withdrawal but are still highly addictive. • Psychological and behavioral components also play a major role in addiction. Key Takeaway: • The physical dependence model explains addiction as driven by avoiding withdrawal symptoms, but it cannot fully explain long-term craving or relapse—suggesting addiction is more than just physical dependence.

Answer 12

Key Findings: • The Experiment: • Rats were trained to press a lever to self-administer a drug (e.g., heroin or cocaine) directly into their bloodstream. • They continued pressing the lever repeatedly, even without any withdrawal symptoms present. • Some rats chose drugs over food or social interaction, highlighting compulsive drug-seeking. • What It Shows: • Supports the Positive Reward Model (正性奖赏模型): • Drug use is driven by the pleasurable, reinforcing effects of the drug (the “high”). • Addiction is more about seeking reward, not just avoiding withdrawal. • Challenges the Physical Dependence Model: • Rats were not using the drug to escape withdrawal—they were motivated by the drug’s rewarding effects, even in its absence. Key Takeaway: • The rat self-administration study supports the positive reward model—showing that addiction is driven by reward-seeking behavior, not merely by avoiding withdrawal.

Answer 13

Key Findings: • Dopamine (多巴胺) • A key neurotransmitter involved in reward, motivation, and reinforcement. • Released in response to natural rewards (e.g., food, social interaction) and drugs of abuse. • Nucleus Accumbens (伏隔核) • A core part of the mesolimbic dopamine system, often called the brain’s reward center. • Receives dopamine input from the ventral tegmental area (VTA). • Activation of the nucleus accumbens reinforces behaviors that lead to dopamine release. • In Addiction: • Drugs like cocaine, nicotine, opioids, and alcohol cause excessive dopamine release in the nucleus accumbens. • This leads to strong reinforcement, promoting repeated use. • Over time, the brain becomes less sensitive to natural rewards, increasing reliance on drugs. Key Takeaway: • Dopamine release in the nucleus accumbens reinforces drug-taking behavior, making it a central mechanism in the development of addiction.

Answer 14

Key Findings: • Purpose of the Study: • To test whether activating dopamine pathways alone is sufficient to drive drug-seeking behavior. • Method (Using Optogenetics): • Researchers artificially stimulated dopamine neurons in the VTA that project to the nucleus accumbens. • Mice were given a lever that would trigger this stimulation. • Results: • Mice learned to press the lever repeatedly, even in the absence of any actual drug. • The behavior mimicked compulsive drug-seeking, showing addiction-like behavior. • Conclusion: • Artificial dopamine activation alone was sufficient to drive reinforcement and habit formation. • Supports the idea that dopamine release in the reward circuit can itself create addictive behavior. Key Takeaway: • Pascoli et al. (2015) showed that directly activating dopamine pathways is sufficient to trigger drug-like reinforcement, proving dopamine’s central role in driving addiction.

Answer 15

Key Findings: • Punishment Phase: • After mice learned to press a lever for dopamine stimulation, researchers introduced a mild foot shock each time the lever was pressed. • This tested whether mice would stop the behavior when facing negative consequences. • Results – Resistance to Punishment: • Despite the foot shock, many mice continued pressing the lever for dopamine pathway stimulation. • This reflects compulsive-like behavior — continuing to seek reward even when it causes harm. • Mimics real-life addiction, where individuals persist in drug use despite negative outcomes (e.g., health issues, social harm). Key Takeaway: • Pascoli et al. (2015) showed that dopamine-driven behavior can persist even in the face of punishment, supporting the idea that addiction involves compulsive and punishment-resistant brain mechanisms.

Answer 16

Key Findings: • Baseline (基线设定): • Mice were trained to press a lever to receive optogenetic activation of dopamine neurons (VTA to nucleus accumbens). • Once they learned this behavior, lever pressing was extinguished by removing the stimulation (no reward when pressing). • This created a baseline of no responding, simulating abstinence or recovery. • Relapse Test: • After extinction, the researchers reactivated the dopamine pathway briefly. • This reinstated the lever-pressing behavior, even though no actual drug or reward was given. • Mice relapsed into the same compulsive seeking, triggered by dopamine activation alone. • Implication: • Demonstrates that dopamine pathway reactivation is sufficient to cause relapse. • Mimics how drug cues or stress might reawaken drug-seeking in human addiction. • Suggests that addiction is deeply encoded in brain circuitry, not just a behavioral habit. Key Takeaway: • Pascoli et al. (2015) showed that even after extinction, reactivating dopamine pathways can trigger relapse, highlighting how vulnerable the brain remains to falling back into addictive behaviors.

Answer 17

Key Findings: • “Wanting” ≠ “Liking” • Wanting refers to motivation and craving, often driven by cues and impulsivity, not conscious choice. • Liking refers to the pleasurable sensation itself. • You can want something without liking it (e.g., in addiction). • Two types of “wanting”: • Goal-directed wanting: Based on conscious intention. • Cue-triggered wanting: Automatic, impulsive, driven by sensitized brain pathways. • Role of Dopamine • Dopamine depletion doesn’t reduce pleasure (liking) but does reduce motivation to seek reward (wanting). • Dopamine is released in the mesolimbic system (e.g., VTA → nucleus accumbens) and becomes sensitized by repeated cue exposure. • Incentive Sensitization • Cues (not drugs themselves) become hyper-salient over time. • Triggers intense “wanting” responses, even if the drug no longer brings pleasure. • Explains relapse, craving, and compulsive use. • Beyond Drugs • Same mechanism applies to gambling, porn, food addiction, etc. • Tolerance develops to the drug’s effect, but sensitization develops to environmental cues. Key Takeaway: • Incentive Sensitization Theory explains addiction as cue-triggered “wanting” that is independent of pleasure. Dopamine sensitization drives compulsive behavior across drug and non-drug addictions.

Answer 18

Key Findings: • Addiction = Brain Disease • Addiction causes long-term neuroplastic changes in key brain circuits, not just behavioral choices. • It affects regions for reward (dopamine, glutamate systems), stress, and executive control (prefrontal cortex). • Three Key Stages of Addiction: 1. Binge/Intoxication – drug causes strong dopamine release, cues become conditioned. 2. Withdrawal/Negative Affect – natural rewards lose meaning; stress systems (amygdala) become overactive. 3. Preoccupation/Anticipation (Craving) – prefrontal cortex function is impaired, leading to poor decision-making and loss of control. • Cue-Triggered Dopamine: • Over time, dopamine spikes shift from drug to drug-predictive cues, driving compulsive seeking behavior. • Reduced Dopamine with Addiction: • In addicted brains, drugs cause less dopamine release than in healthy brains → explains tolerance, less pleasure, reduced motivation for normal rewards. • Neuroplasticity: • Long-term drug use alters glutamate and dopamine signaling, especially in prefrontal cortex, amygdala, hippocampus, and nucleus accumbens. • Treatment and Prevention: • Emphasizes medical and behavioral interventions over punishment. • Medications (e.g., methadone, buprenorphine, naltrexone) and behavioral therapy can restore function. • Early prevention should focus on teaching self-regulation, stress control, and emotional development, especially in adolescents. • Stigma and Policy: • Framing addiction as a disease helps reduce stigma and supports policies that promote treatment over incarceration. • Supports insurance parity laws and integration of addiction care into primary healthcare. Key Takeaway: • Addiction alters brain circuits involved in reward, stress, and self-control. Framing it as a brain disease shifts the focus from moral blame to science-based treatment and recovery support.

Answer 19

Key Findings: • 1. Disease Model（疾病模型） • Addiction is a brain disease involving structural and functional changes. • Advocates medical treatment and reducing stigma. • 2. Moral Model（道德模型） • Addiction is due to poor moral choices or lack of willpower. • Leads to stigma, shame, and punitive responses, not support. • 3. Physical Dependence Model（生理依赖模型） • Focuses on withdrawal symptoms as the reason people continue using drugs. • Addiction = avoiding discomfort. • 4. Positive Reward Model（奖赏模型） • Drugs activate the reward system, causing pleasure that reinforces continued use.

Answer 20

With repeated use, the reward pathway becomes sensitized, especially to external cues associated with the drug. • This causes increased “wanting” (motivation to seek) without increased “liking” (pleasure). • Explains craving and relapse, even when the drug no longer feels good. Key Takeaway: • Addiction is best explained by combining brain-based models (e.g., disease, sensitization) and motivational mechanisms. “Wanting” can persist without “liking,” driven by cue-triggered dopamine release.