LECTURE 1
A lot of people use substances despite harmful effects:
a) To feel good → Uppers may lead to feeling powerful, energetic and confident. Downers tend to provide feelings of relaxation
and satisfaction.
b) To feel better → People may use substances to reduce social anxiety or stress when they connect with others or to reduce
symptoms linked to trauma or depression
c) To do better → Pressure to perform leads many people to use chemicals to keep going
d) To explore → Some people have a higher need to try something new and take risks. These people may use drugs to discover
new experiences, feelings or understandings.
The shift from use to abuse is when at some point after continued repetition of voluntary drug-taking, the drug 'user' loses the voluntary
ability to control its use. At that point, the 'drug misuser' becomes 'drug addicted' and there is a compulsive, often overwhelming
involuntary aspect to continuing drug use and to relapse after a period of abstinence.
- According to the DSM to qualify as abuse, a problematic pattern of substance use is required, leading to clinically significant
limitations or suffering.
DSM CRITERIA
1. Taking the substance in larger amounts or for longer than you're meant to
2. Wanting to cut down or stop using the substance but not managing to
3. Spending a lot of time getting, using, or recovering from use of the substance
4. Cravings and urges to use the substance
5. Not managing to do what you should at work, home, or school because of substance use
6. Continuing to use, even when it causes problems in relationships
7. Giving up important social, occupational, or recreational activities because of substance use
8. Using substances again and again, even when it puts you in danger
9. Continuing to use, even when you know you have a physical or psychological problem that could have been caused or made
worse by the substance
10. Needing more of the substance to get the effect you want (tolerance)
11. Development of withdrawal symptoms, which can be relieved by taking more of the substance
Fortunately, only a minority of people who use develops a substance abuse disorder. 17% of people in the Netherlands suffer from
substance abuse at some point in their lives. → 12.8% alcohol, 6.6% drugs. No single factor can predict whether a certain individual
will develop substance abuse. The interplay between genetic, environmental and developmental factors influences risk for addiction.
The more risk factors, the greater the chance that alcohol/drug use spirals out of control. The more protective factors, the greater the
resilience of the individual against developing an addiction.
- There is a vicious cycle, the negative consequences of alcohol/drug abuse maintain or worsen the abuse.
Sociodemographic factors
- Younger age
- Gender: men at greater risk
- Living alone
- Being unemployed
- Very high degree of urbanization
*Unrelated to income or country of origin
Risk factors
a) Early aggressive behavior in childhood
b) Early drug use ( → shows importance of prevention)
c) Lack of parental supervision
d) Substance abuse by caregivers
e) Low refusal skills
f) Poor social skills
g) Drug availability at school
h) Community poverty
i) Difference in type of drugs and manner of administration, especially administration through ingesting or injecting
j) Genetic predispositions
k) Personality traits: sensating-seeking, impulsivity, difficulty with self-regulation
l) Comorbidity with other mental health issues such as depression, early childhood trauma, anxiety, ADHD
Protective factors
a) Self-efficacy (belief in self-control)
b) Academic performance
c) Parental monitoring and support
d) Positive relationships with peers
e) School anti-drug policies
f) Neighborhood resources
1
,According to the NEMESIS study, people with substance abuse make the least use of mental health services compared to other mental
disorders. Barriers to seeking treatment:
1. Attitudinal → I thought it would get better; I thought I could handle it myself; I did not think anyone could help
2. Readiness for change → I thought the problem was not serious enough (motivational interviewing could help)
3. Stigma → Afraid of other people's opinions
4. Financial/cost
5. Structural → I did not know where to go and how to get there
The treatment efficacy is low → Those who do get treatment have a high relapse rate between 40-60%. A few of the most common
triggers into relapse include:
- Returning to a particular place or seeing a person associated with drug use
- Stressful circumstances that trigger drug or alcohol use
- Pre-existing emotional or mental health challenges
Prominent critics of the brain disease model:
- Addictive behavior is 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
- Most people beat addiction by working really hard at it, only if we could say the same about medical diseases.
Why and for whom does it spiral out of control?
1. Module 1 → The role of motivation processes
2. Module 2 → The role of habits and impaired cognitive control functions
Strong craving is common across substance use disorders, and is thought to play an important role in relapse.
Microdialysis studies show that natural rewards (presentation of food) lead to increased
release of dopamine levels in the nucleus accumbens which shows the craving. Substances of
abuse also lead to increased dopamine release in the nucleus accumbens. But much more so
than natural reinforcers.
- While natural reinforcers lead to a modest increase in DA release, substances of
abuse strongly increase it (above 100% baselevel).
- When triggered by external stimuli that drugs will become available such in craving
the dopamine release is even higher (Pavlovian learning)
= A technique used to measure concentrations of molecules in the extracellular fluid of tissues.
It's commonly used in neuroscience and pharmacology research to study neurotransmitters,
drugs, and other molecules in vivo.
- A microdialysis probe with a semipermeable membrane is surgically implanted into
the NAcc of the rat under anesthesia. After implantation, the probe is perfused with a
physiological solution to allow the tissue to equilibrate. Perfusion continues, and
samples of the dialysate are collected at regular intervals (e.g., every 15-30 minutes).
- Increased dopamine release in the NAcc is associated with rewarding experiences
and reinforces behaviors that lead to reward. Elevated dopamine levels in the NAcc
in response to drugs of abuse may contribute to the addictive properties of these
substances.
Mesolimbic pathway
Striatum → A small group of subcortical structures in the basal ganglia, including:
1. Caudate
2. Putamen
3. Nucleus accumbens (often referred to as ventral striatum) → Important for craving!
- Dopamine neurons in the ventral tegmental area (VTA) project to the nucleus accumbens (Nacc; ventral striatum)
PET studies show lower density of dopamine (DA) D2 receptors in addicted individuals, relative to controls. → Very important finding
for brain disease model
Homeostatic account = These patterns result from homeostasis-compensatory brain changes after chronic drug use in order to lower
dopamine (DA) transmission: Balance is established through downregulation of D2 receptors.
- Chronic drug use often leads to increased dopamine release or decreased dopamine reuptake, resulting in elevated dopamine
levels in the NAcc. In response to the increased dopamine activity, the brain downregulates D2 receptors to establish a new
balance or homeostasis.
Increased dopamine activity due to drugs → Decrease of dopamine D2 receptors
- Downregulation of D2 receptors may lead to decreased sensitivity to natural rewards, contributing to symptoms like anhedonia
(lack of pleasure) and dysphoria (general dissatisfaction or unease). As the brain adjusts to chronic drug use by reducing D2
receptor sensitivity, individuals may require increasing amounts of the drug to achieve the same level of pleasure or reward,
leading to escalated drug consumption.
2
, - 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. These studies show indeed that chronic cocaine use can cause D2
receptors downregulation.
- D2 receptor density can recover (increase) following a period of abstinence.
- However, 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.
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 no sufficient) → So
there is evidence for both directions.
Pavlovian/classical conditioning = A change in behavior due to experience with a
relationship between a (neutral) conditioned stimulus (CS) and a (motivationally
relevant) unconditioned stimulus (US).
- To investigate this, in cue reactivity fMRI studies, participants are shown
images of alcohol and drugs, as well as neutral images (e.g. nonalcoholic
drinks).
- To reveal brain activity reflecting cue reactivity to alcohol/drug images, the
BOLD (blood-oxygenation-level-dependent) signal is contrasted with that
during the 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 (and next to other regions,
including ventromedial prefrontal cortex/orbitofrontal cortex etc)
- Studies have shown that this correlates with cue-induced self-reported craving
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)
- Surprisingly, motivationally significant events (unpredicted USs and
CSs) are reflected in phasic dopamine firing.
Phasic dopamine firing is often observed in response to unpredicted rewards
or positive outcomes (USs) in classical and operant conditioning paradigms.
Over time, through associative learning, neutral stimuli (CSs) that predict the
occurrence of a reward can also lead to phasic dopamine firing. Dopamine neurons are thought to encode a "reward prediction error,"
which is the difference between the expected and actual outcomes.
Positive prediction errors (better than expected outcomes) lead to increased dopamine firing, whereas negative prediction errors
(worse than expected outcomes) result in decreased dopamine firing or inhibition.
- 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 → It functions as a teaching signal
- Once the 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).
Difference in phasic dopamine signal in NAc and consequences for learning
is that in natural reinforcer after a while the food consumption does not
spike the dopamine, only the cue presentation does. However, in drugs it
has been shown that even after a while the drug infusion still spikes the
dopamine levels to an extreme level.
Temporal difference (aberrant learning) account = Over repeated drug
use, the repetition of these DA signals would continue to reinforce
drug-related cues and actions to pathological levels.
- In natural reinforcers, the dopamine response shifts from the
primary reinforcer to predictive cues with repeated exposure.
However, drugs maintain their ability to spike dopamine levels
even after repeated use. This difference leads to aberrant learning
where drug-related cues and actions are pathologically reinforced,
contributing to compulsive drug-seeking behavior and addiction.
Berridge → I believe the mesolimbic suppressions (including D2 receptor downregulation in response to excessive dopamine levels),
while mechanisms of tolerance and withdrawal, are relatively temporary, more a consequence than cause of drug taking, and not the
essence of addiction.
3
, Incentive-sensitization theory = A pathological motivation for drugs (together with impaired cognitive control) is the core problem in
addiction. (Berridge & Robinson)
- Repeated substance abuse leads to a decrease in liking (the hedonic experience during consumption of the substance) →
Always chasing the first high
- At the same time, however, according to I-S theory, (cue-triggered) wanting of the substance increases → craving
Wanting = The extreme craving that does not have to be experienced consciously, and that is triggered especially by
drug-associated cues (different from day to day wanting)
Incentive sensitization can be measured using behavioral tasks that assess cue reactivity, as well as neuroimaging techniques like
fMRI to examine brain responses to drug-related cues.
At the neurobiological level the I-S theory states that repeated drug use leads to changes in the mesolimbic dopamine (DA) system that
plays a role in motivational and Pavlovian processes (craving). Specifically, this system becomes sensitized (hyperreactive) to the
incentive effects of drugs and drug-associated cues.
At the behavioral level the I-S theory states that the incentive salience of drug-associated stimuli increases in substance abuse. This is
expressed behaviorally most prominently in the following three ways:
1. Drug-associated stimuli elicit attention and approach towards them (they become wanted), acting as 'motivational magnets' →
any stimulus in environment that is associated with the ritual of drug use e.g. needle
2. Drug-associated stimuli become reinforcers in their own right → The people you normally use with you actually start to like
more and hang out with more
3. Drug-associated stimuli (and drugs) can induce relapse (after a period of abstinence) → Reinstatement
● Furthermore (sort of a 4th way not really), incentive sensitization is expressed behaviorally in an increasing
willingness/motivation to work for the drug.
1. Drug-associated cues become motivational magnets
= 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
- Studied through the conditioned place preference paradigm → An increase in
time spent in the drug-paired chamber indicates that the drug has rewarding or
reinforcing effects, as the animal develops a preference for the environment
associated with the drug.
- Dopamine has been implicated in drug-induced conditioned place
preference. Neuronal activation in the ventral tegmental area (VTA), a
brain region where dopamine neurons are expressed, is
necessary for the acquisition of drug CPP.
- This can also be studied in humans!
2. Drug-associated cues become (conditioned) reinforcers in their own right
= Conditioned reinforcement occurs when a stimulus (CS) has acquired the
capacity to reinforce behaviors through its learned CS-US association with a drug
(US).
- Studied through conditioned reinforcement paradigm.
Furthermore, conditioned reinforcement is potentiated by
stimulating dopamine release in the nucleus accumbens. (So
strongly linked to dopamine function)
3. Drugs reinstate drug seeking (relapse)
Conditioned reinstatement = 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
- Incubation of craving = Even increases in drug seeking have
been observed in animals after a period of extinction… craving
may increase during extinction
- Next to conditioned reinstatement by drug-associated cues (CS)
there is also drug reinstatement (a single dose of drug/drink
leads to a full-blown relapse) and stress reinstatement
- Experimental studies into different forms of reinstatement show
that reinstatement can be prevented by systemic or local
manipulation of the ventral tegmental area (VTA) and nucleus
accumbens (i.e. mesolimbic pathway), thereby implicating the
mesolimbic pathway in reinstatement.
4
A lot of people use substances despite harmful effects:
a) To feel good → Uppers may lead to feeling powerful, energetic and confident. Downers tend to provide feelings of relaxation
and satisfaction.
b) To feel better → People may use substances to reduce social anxiety or stress when they connect with others or to reduce
symptoms linked to trauma or depression
c) To do better → Pressure to perform leads many people to use chemicals to keep going
d) To explore → Some people have a higher need to try something new and take risks. These people may use drugs to discover
new experiences, feelings or understandings.
The shift from use to abuse is when at some point after continued repetition of voluntary drug-taking, the drug 'user' loses the voluntary
ability to control its use. At that point, the 'drug misuser' becomes 'drug addicted' and there is a compulsive, often overwhelming
involuntary aspect to continuing drug use and to relapse after a period of abstinence.
- According to the DSM to qualify as abuse, a problematic pattern of substance use is required, leading to clinically significant
limitations or suffering.
DSM CRITERIA
1. Taking the substance in larger amounts or for longer than you're meant to
2. Wanting to cut down or stop using the substance but not managing to
3. Spending a lot of time getting, using, or recovering from use of the substance
4. Cravings and urges to use the substance
5. Not managing to do what you should at work, home, or school because of substance use
6. Continuing to use, even when it causes problems in relationships
7. Giving up important social, occupational, or recreational activities because of substance use
8. Using substances again and again, even when it puts you in danger
9. Continuing to use, even when you know you have a physical or psychological problem that could have been caused or made
worse by the substance
10. Needing more of the substance to get the effect you want (tolerance)
11. Development of withdrawal symptoms, which can be relieved by taking more of the substance
Fortunately, only a minority of people who use develops a substance abuse disorder. 17% of people in the Netherlands suffer from
substance abuse at some point in their lives. → 12.8% alcohol, 6.6% drugs. No single factor can predict whether a certain individual
will develop substance abuse. The interplay between genetic, environmental and developmental factors influences risk for addiction.
The more risk factors, the greater the chance that alcohol/drug use spirals out of control. The more protective factors, the greater the
resilience of the individual against developing an addiction.
- There is a vicious cycle, the negative consequences of alcohol/drug abuse maintain or worsen the abuse.
Sociodemographic factors
- Younger age
- Gender: men at greater risk
- Living alone
- Being unemployed
- Very high degree of urbanization
*Unrelated to income or country of origin
Risk factors
a) Early aggressive behavior in childhood
b) Early drug use ( → shows importance of prevention)
c) Lack of parental supervision
d) Substance abuse by caregivers
e) Low refusal skills
f) Poor social skills
g) Drug availability at school
h) Community poverty
i) Difference in type of drugs and manner of administration, especially administration through ingesting or injecting
j) Genetic predispositions
k) Personality traits: sensating-seeking, impulsivity, difficulty with self-regulation
l) Comorbidity with other mental health issues such as depression, early childhood trauma, anxiety, ADHD
Protective factors
a) Self-efficacy (belief in self-control)
b) Academic performance
c) Parental monitoring and support
d) Positive relationships with peers
e) School anti-drug policies
f) Neighborhood resources
1
,According to the NEMESIS study, people with substance abuse make the least use of mental health services compared to other mental
disorders. Barriers to seeking treatment:
1. Attitudinal → I thought it would get better; I thought I could handle it myself; I did not think anyone could help
2. Readiness for change → I thought the problem was not serious enough (motivational interviewing could help)
3. Stigma → Afraid of other people's opinions
4. Financial/cost
5. Structural → I did not know where to go and how to get there
The treatment efficacy is low → Those who do get treatment have a high relapse rate between 40-60%. A few of the most common
triggers into relapse include:
- Returning to a particular place or seeing a person associated with drug use
- Stressful circumstances that trigger drug or alcohol use
- Pre-existing emotional or mental health challenges
Prominent critics of the brain disease model:
- Addictive behavior is 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
- Most people beat addiction by working really hard at it, only if we could say the same about medical diseases.
Why and for whom does it spiral out of control?
1. Module 1 → The role of motivation processes
2. Module 2 → The role of habits and impaired cognitive control functions
Strong craving is common across substance use disorders, and is thought to play an important role in relapse.
Microdialysis studies show that natural rewards (presentation of food) lead to increased
release of dopamine levels in the nucleus accumbens which shows the craving. Substances of
abuse also lead to increased dopamine release in the nucleus accumbens. But much more so
than natural reinforcers.
- While natural reinforcers lead to a modest increase in DA release, substances of
abuse strongly increase it (above 100% baselevel).
- When triggered by external stimuli that drugs will become available such in craving
the dopamine release is even higher (Pavlovian learning)
= A technique used to measure concentrations of molecules in the extracellular fluid of tissues.
It's commonly used in neuroscience and pharmacology research to study neurotransmitters,
drugs, and other molecules in vivo.
- A microdialysis probe with a semipermeable membrane is surgically implanted into
the NAcc of the rat under anesthesia. After implantation, the probe is perfused with a
physiological solution to allow the tissue to equilibrate. Perfusion continues, and
samples of the dialysate are collected at regular intervals (e.g., every 15-30 minutes).
- Increased dopamine release in the NAcc is associated with rewarding experiences
and reinforces behaviors that lead to reward. Elevated dopamine levels in the NAcc
in response to drugs of abuse may contribute to the addictive properties of these
substances.
Mesolimbic pathway
Striatum → A small group of subcortical structures in the basal ganglia, including:
1. Caudate
2. Putamen
3. Nucleus accumbens (often referred to as ventral striatum) → Important for craving!
- Dopamine neurons in the ventral tegmental area (VTA) project to the nucleus accumbens (Nacc; ventral striatum)
PET studies show lower density of dopamine (DA) D2 receptors in addicted individuals, relative to controls. → Very important finding
for brain disease model
Homeostatic account = These patterns result from homeostasis-compensatory brain changes after chronic drug use in order to lower
dopamine (DA) transmission: Balance is established through downregulation of D2 receptors.
- Chronic drug use often leads to increased dopamine release or decreased dopamine reuptake, resulting in elevated dopamine
levels in the NAcc. In response to the increased dopamine activity, the brain downregulates D2 receptors to establish a new
balance or homeostasis.
Increased dopamine activity due to drugs → Decrease of dopamine D2 receptors
- Downregulation of D2 receptors may lead to decreased sensitivity to natural rewards, contributing to symptoms like anhedonia
(lack of pleasure) and dysphoria (general dissatisfaction or unease). As the brain adjusts to chronic drug use by reducing D2
receptor sensitivity, individuals may require increasing amounts of the drug to achieve the same level of pleasure or reward,
leading to escalated drug consumption.
2
, - 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. These studies show indeed that chronic cocaine use can cause D2
receptors downregulation.
- D2 receptor density can recover (increase) following a period of abstinence.
- However, 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.
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 no sufficient) → So
there is evidence for both directions.
Pavlovian/classical conditioning = A change in behavior due to experience with a
relationship between a (neutral) conditioned stimulus (CS) and a (motivationally
relevant) unconditioned stimulus (US).
- To investigate this, in cue reactivity fMRI studies, participants are shown
images of alcohol and drugs, as well as neutral images (e.g. nonalcoholic
drinks).
- To reveal brain activity reflecting cue reactivity to alcohol/drug images, the
BOLD (blood-oxygenation-level-dependent) signal is contrasted with that
during the 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 (and next to other regions,
including ventromedial prefrontal cortex/orbitofrontal cortex etc)
- Studies have shown that this correlates with cue-induced self-reported craving
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)
- Surprisingly, motivationally significant events (unpredicted USs and
CSs) are reflected in phasic dopamine firing.
Phasic dopamine firing is often observed in response to unpredicted rewards
or positive outcomes (USs) in classical and operant conditioning paradigms.
Over time, through associative learning, neutral stimuli (CSs) that predict the
occurrence of a reward can also lead to phasic dopamine firing. Dopamine neurons are thought to encode a "reward prediction error,"
which is the difference between the expected and actual outcomes.
Positive prediction errors (better than expected outcomes) lead to increased dopamine firing, whereas negative prediction errors
(worse than expected outcomes) result in decreased dopamine firing or inhibition.
- 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 → It functions as a teaching signal
- Once the 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).
Difference in phasic dopamine signal in NAc and consequences for learning
is that in natural reinforcer after a while the food consumption does not
spike the dopamine, only the cue presentation does. However, in drugs it
has been shown that even after a while the drug infusion still spikes the
dopamine levels to an extreme level.
Temporal difference (aberrant learning) account = Over repeated drug
use, the repetition of these DA signals would continue to reinforce
drug-related cues and actions to pathological levels.
- In natural reinforcers, the dopamine response shifts from the
primary reinforcer to predictive cues with repeated exposure.
However, drugs maintain their ability to spike dopamine levels
even after repeated use. This difference leads to aberrant learning
where drug-related cues and actions are pathologically reinforced,
contributing to compulsive drug-seeking behavior and addiction.
Berridge → I believe the mesolimbic suppressions (including D2 receptor downregulation in response to excessive dopamine levels),
while mechanisms of tolerance and withdrawal, are relatively temporary, more a consequence than cause of drug taking, and not the
essence of addiction.
3
, Incentive-sensitization theory = A pathological motivation for drugs (together with impaired cognitive control) is the core problem in
addiction. (Berridge & Robinson)
- Repeated substance abuse leads to a decrease in liking (the hedonic experience during consumption of the substance) →
Always chasing the first high
- At the same time, however, according to I-S theory, (cue-triggered) wanting of the substance increases → craving
Wanting = The extreme craving that does not have to be experienced consciously, and that is triggered especially by
drug-associated cues (different from day to day wanting)
Incentive sensitization can be measured using behavioral tasks that assess cue reactivity, as well as neuroimaging techniques like
fMRI to examine brain responses to drug-related cues.
At the neurobiological level the I-S theory states that repeated drug use leads to changes in the mesolimbic dopamine (DA) system that
plays a role in motivational and Pavlovian processes (craving). Specifically, this system becomes sensitized (hyperreactive) to the
incentive effects of drugs and drug-associated cues.
At the behavioral level the I-S theory states that the incentive salience of drug-associated stimuli increases in substance abuse. This is
expressed behaviorally most prominently in the following three ways:
1. Drug-associated stimuli elicit attention and approach towards them (they become wanted), acting as 'motivational magnets' →
any stimulus in environment that is associated with the ritual of drug use e.g. needle
2. Drug-associated stimuli become reinforcers in their own right → The people you normally use with you actually start to like
more and hang out with more
3. Drug-associated stimuli (and drugs) can induce relapse (after a period of abstinence) → Reinstatement
● Furthermore (sort of a 4th way not really), incentive sensitization is expressed behaviorally in an increasing
willingness/motivation to work for the drug.
1. Drug-associated cues become motivational magnets
= 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
- Studied through the conditioned place preference paradigm → An increase in
time spent in the drug-paired chamber indicates that the drug has rewarding or
reinforcing effects, as the animal develops a preference for the environment
associated with the drug.
- Dopamine has been implicated in drug-induced conditioned place
preference. Neuronal activation in the ventral tegmental area (VTA), a
brain region where dopamine neurons are expressed, is
necessary for the acquisition of drug CPP.
- This can also be studied in humans!
2. Drug-associated cues become (conditioned) reinforcers in their own right
= Conditioned reinforcement occurs when a stimulus (CS) has acquired the
capacity to reinforce behaviors through its learned CS-US association with a drug
(US).
- Studied through conditioned reinforcement paradigm.
Furthermore, conditioned reinforcement is potentiated by
stimulating dopamine release in the nucleus accumbens. (So
strongly linked to dopamine function)
3. Drugs reinstate drug seeking (relapse)
Conditioned reinstatement = 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
- Incubation of craving = Even increases in drug seeking have
been observed in animals after a period of extinction… craving
may increase during extinction
- Next to conditioned reinstatement by drug-associated cues (CS)
there is also drug reinstatement (a single dose of drug/drink
leads to a full-blown relapse) and stress reinstatement
- Experimental studies into different forms of reinstatement show
that reinstatement can be prevented by systemic or local
manipulation of the ventral tegmental area (VTA) and nucleus
accumbens (i.e. mesolimbic pathway), thereby implicating the
mesolimbic pathway in reinstatement.
4
