Addiction

Addiction

How do we classify drugs?

Definition of Drug:

  • A substance used to bring about a change in some existing process of state (psychological, physical, and biochemical)

  • A chemical entity, other than those providing maintenance of normal health (ex: food) that alters normal biological functioning.

Categorization of Drugs:

  • Drugs are categorized by their behavior and/or pharmacological effects

Stimulants: elevate mood, increase feelings of well-being, enhance energy and alertness. (​​amphetamine, methamphetamine, cocaine)

Depressants: reduce psychological activity often leading to relaxation and sedation. (“antipsychotics”- Zyprexa, “benzos”- Xanax, “barbiturates”- Amytal, alcohol)

Opioids: both prescribed and illegal drugs that are primarily used for pain relief.

Hallucinogens: substances that cause change in perception, mood, and cognitive processes

Psychotherapeutics: medications to treat mental disorders, impacting mood, cognition, and behavior.

  • Categories of drugs often are grouped based on the endogenous neurotransmitters they mimic or directly/indirectly influence release. e.g stimulants (DA), Depressants (GABA), opioids (endogenous opioids


Which Drugs are more commonly abused:

  • Drug use is not the same as drug abuse

Distinction between the two:

  • Drug use is the general consumption of substances, while drug abuse indicates a pattern of compulsive substance use leading to significant adverse consequences in social, occupational, legal, or interpersonal contexts.

Addiction: state of psychological or physical dependence on the use of alcohol or other drugs, equating to substance dependence, potentially extending to behavioral disorders like sexual, internet, and gambling addictions.

Top Abused Drugs:

  • Marijuana

  • Prescription pain relievers

  • Prescription tranquilizers

  • Cocaine

  • Prescription stimulants

3 out of the top 5 abused drugs are regularly prescribed by a physician!!

How do we define drug abuse and addiction?

Clinical definition from DSM- V:

  • Substance use disorder characterized by severity:

  • Mild (2-3 criteria met) moderate (4-5 criteria met) Severe (6+ criteria met)

  • Incorporates distinct terms for each substance and adds criteria for drug craving while excluding legal problems. Legal problems was eliminated from the DSM 5 with the intention of taking away some of the stigma associated with SUD; individuals in lower socioeconomic status are more likely to face legal problems in acquiring drugs. However, addiction does not discriminate on income, status, or population. 

  • Behavioral addictions (includes gambling disorder)

  • Pharmacological definition of Addiction:

focused on a dependence on the substance to feel normal. Pharmacologically, there are compensatory mechanisms and adaptations to chronic administration i.e, changes to normal bodily functions. Changes to neuronal functioning is of particular interest.


Is Addiction a Brain Disease?

  1. Moral model

  • Individuals with addiction are those who choose drugs over responsibilities due to personal morals and weaknesses

  • (Shame for failing, points to their character)

  1. Medical model

  • Considers addiction as a chronic brain disease that complicates an individual's ability to cease using substances.

  • (People are sick, focus on the addiction affecting their physical body)

  1. Biopsychological model

  • Considers addiction as a product of multiple factors, including biological, psychological, and sociocultural influences.

  • (People are complicated, many different factors to consider)

The model we choose decides whether money goes to punishment or to treatment, and it influences policy, stigma, and people’s lives.


How do we study drug use experimentally?

In the US >80% adults have taken addictive drug, but  only 10-20% become addicted. Once addicted, 90% will relapse after abstinence. 

Animal models!!

  • Provide a method to study causal effects due to ethical limitations in human research.

  • Allow access to additional tools and techniques

  • Isolate specific features of addiction such as:

Drug taking behavior, motivation for drug use, resistance to punishment, drug craving and relapse, and sex differences in addiction prevalence and behaviors.

In animals, and in human literature, we see evidence that men and women show differences in drug taking and the transition to addiction. for example, women transition to addiction sooner than men, and women take higher doses than many men, and often experience more negative affect to withdrawal. We must account for these differences. Historically (and still today) male animals are predominantly used as they are viewed as “normal” and females are seen as “complex, confusing” due to their menstrual cycle, but females’ behavior is actually more stable than males…as females have a month long cycle and males have a daily cycle.



Conditioned place preference/ aversion:

A method to see if drugs are rewarding:

  • Split environment with saline on one side, drug injections on the other.

  • During test day, observe the side an animal chooses in the absence of drug injection

Interpretation:

  • Drug is rewarding if animals show a preference for the drug side

  • Drugs are aversive if animals avoid the drug side.

The Conditioned Place Preference/Aversion (CPP/CPA) test measures whether a drug is rewarding or aversive. Animals are placed in two distinct rooms. One room is repeatedly paired with drug injections, the other with control injections. On test day, no drug is given, and the animal can freely explore both rooms. If the animal spends more time in the drug-paired room, the drug is considered rewarding (CPP). If it avoids that room, the drug is aversive (CPA). Researchers can test how dose, antagonists, or other conditions change preference, helping them understand the motivational properties of drugs.



Drug Self- Administration:

Involves animals performing actions for drug rewards:

  • Can vary the requirements for receiving the drug:

    • Fixed Ratio Schedules: Measures the rate of response, e.g., FR1 (one response for the drug) vs. FR5 (five responses for the drug).

    • Progressive Ratio Schedules: Assesses motivation; each subsequent reward requires an increasing number of responses until reaching a breakpoint where responses cease.

    • Analyzes resistance to punishment by pairing drug rewards with aversive stimuli (like foot shocks).

Is this addiction?

No, not entirely!

Limitations of Animal Models:

  • Models do not fully replicate human addiction; researchers create unnatural conditions that bias animals toward drug administration.

  • Factors include:

  • Single housing of animals,

  • Food restriction,

  • Minimal environmental enrichment and stimulation,

  • Limited interaction outside of drug sessions.

  • Raises questions regarding how such circumstances would affect human behavior.

What features of addiction can we model?

Include features such as:

  • Drug-taking behaviors

  • Drug-seeking behaviors, indicating compulsive searching even when drugs are unavailable.

  • Resistance to punishment: an analysis of how much adversity animals will endure.

  • Escalation of motivation: evaluates how hard individuals are willing to work for drugs.

  • Relapse occurrences: where exposure to drugs or drug-related cues may trigger a return to use.

Theories of addiction- what is the role of dopamine?

  • Theories of addiction primarily focus on dopamine functioning in the brain.

  • Dopamine Signaling Pathway:

    • Involves the ventral tegmental area (VTA) signaling to the nucleus accumbens (NAc), which is implicated in the rewarding effects of drugs and other rewards.

    • Increase in dopamine from VTA to NAc is observed during drug use, often producing heightened pleasure and reward sensations.

  • Many drugs of abuse release dopamine directly (bind to receptor) or indirectly (blocking reuptake) or by acting on other receptors that ultimately act on DA neurons. Also, dopamine in SN leads to movement, (dopamine in VTA (same level midbrain structure) in motivation)  

ALLOSTASIS MODEL - WITHDRAWAL AVOIDANCE

  • The allostasis model says compulsive drug use happens because people want to escape the negative emotional state of withdrawal. 

  • Withdrawal lowers dopamine (DA) and mood, so using the drug again temporarily fixes that low mood—creating a cycle of repeated use. 

Key Problems / Critiques: 

  • Craving doesn’t match withdrawal: cravings are often highest right after taking the drug, when drug levels are highest (ex: cocaine). 

  • Withdrawal doesn’t predict relapse: people relapse even when they’re not in withdrawal. 

  • Drug cues raise DA, not lower it, which contradicts the idea that low DA causes craving. 

  • Mood relief explains some use, but not all—the model can’t fully account for craving patterns or cue-driven relapse.

ANHEDONIA THEORY OF ADDICTION

  • Suggests that dopamine is responsible for generating pleasure (hedonia) in the brain.

  • It posits that drugs are addictive because they stimulate dopamine systems, leading to heightened pleasure responses:

    • Individuals with substance use disorders (SUD) may have naturally low DA, leading them to seek drugs to elevate their DA levels.

  • Supporting Evidence:

    • Many drugs of abuse induce euphoria, often through increased DA release.

BUT DOES DOPAMINE GENERATE PLEASURE?

  • Asking how to measure 'liking' in rats is challenging; researchers often use taste reactivity tests.

  • Key Findings:

    • Alterations in DA signaling do not significantly impact hedonic reactions.

    • Evidence shown from experiments involving DA lesions and the use of dopamine antagonists or agonists.

Taste Reactivity Test: A method for measuring hedonic impact (“liking”) using automatic facial/oral reactions to tastes in animals. Positive reactions (sweet): lip licking, tongue protrusions Negative reactions (bitter): gaping, head shakes Key finding: Dopamine depletion does NOT reduce positive “liking” reactions. Increasing dopamine does NOT increase “liking.” Conclusion: Dopamine does not mediate pleasure — it mediates “wanting” (incentive salience).

ISSUES WITH ANHEDONIA THEORY

  • Complexities:

    • Dopamine release is often observed prior to drug administration, indicating other factors are at play.

    • Dopamine involvement in aversive motivation complicates pleasure-centric views.

    • Disruption of dopamine does not inhibit euphoric effects, arguing against a straightforward hedonic link.

INCENTIVE SENSITIZATION THEORY (IST) OF ADDICTION

  • Proposes that compulsive cravings and relapse are driven by excessive ‘wanting’ rather than ‘liking’:

    • Drugs can incite pleasure; however, it is the desire or craving that fuels the addiction process.

  • Mechanism:

    • Dopamine release is linked to excessive wanting through sensitization of the DA system, with cues associated with drugs becoming exceedingly potent motivational triggers.

  • Significance:

    • Uncontrollable wanting for drugs does not necessarily correlate with the liking of drug effects.

    • Explains the high rates of relapse even after long periods of abstinence, with enduring dopamine sensitization effects.


Sensitization: A drug effect where repeated drug exposure produces an increasingly stronger behavioral response over time. Example (psychomotor sensitization): After repeated stimulant doses, animals show greater locomotor activity (run more) to the same dose. This supports the idea that drugs cause long-lasting changes that increase “wanting”.

WHAT IS SENSITIZATION?

  • Defined as psychomotor activity, or drug-induced increases in motor behavior influenced by psychological states.

  • Drug-Induced Psychomotor Sensitization:

    • A method to assess the capacity of drugs to produce progressively increasing behavioral changes through repeated exposure.

    • Locomotor Activity is considered an indirect model of the addictive process.

  • This sensitization explains the increasingly greater effects of a drug with continued exposure.

INCENTIVE SENSITIZATION SUPPORT AND ISSUES

  • Support:

    • Cravings persist even long after withdrawal, with the highest cravings generally occurring during active drug use.

    • Drugs with smaller withdrawal symptoms (like amphetamines and cocaine) often show greater addictiveness.

    • Nicotine is particularly addictive despite being less euphoric compared to other drugs.

    • Dopamine does not appear to control liking, which complicates simplified associations between dopamine and pleasure.

  • Issues:

    • Chronic drug use is frequently linked to low dopamine levels—whether this is a causative or resultant issue is unclear.

    • Questions arise about why sensitization might not lead to excessive wanting for other rewarding experiences (food, sex, thrill-seeking).

SUMMARY

  • Substance Use Disorders are qualified based on the guidelines established by the DSM (Diagnostic and Statistical Manual of Mental Disorders) versions from the APA.

  • Animal models are crucial for understanding the neurological changes related to addiction.

  • Major theories of addiction focus on the functionality of dopamine, emphasizing:

    • Allostasis Model

    • Withdrawal Avoidance

    • Anhedonia Theory

    • Role of pleasure in addiction

    • Incentive Sensitization Theory

    • Sensitized wanting system for drugs and its implications for relapse and cravings.