Addiction
Case 3
Addiction is a brain disease
Problem statement: “?”
Learning goals:
I. How does the reward system work normally and within addiction?
II. What is the dopaminergic pathway of addiction?
III. What is the difference between a healthy and a drug addicted brain?
IV. What determines the maintenance of the addiction?
V. What neurobiological treatments are there for addiction?
BDMA: Brain Disease Model of Addiction " addictive behaviors change the brain in various ways,
which makes repeated relapse more likely, including changes in reward sensitivity, stress reactivity
and negative affect, and reduced cognitive control and self-regulation.
Addiction is a chronic disease.
How does the reward system work normally and within addiction? i
Chemicals in drugs boost the activity of the brain’s reward system ultimately.
A complex circuit of neurons which gives pleasure and encourages to repeat the activity.
o The reward by drug-stimulation is greater than any neutral reward.
The pathway extends from the dopamine-producing nerve cells (neurons) of the ventral
tegmental area (VTA) to dopamine-sensitive cells in the nucleus accumbens.
= The mesocorticolimbic dopamine system
o Stimulation of this pathway by cues reinforces drug-behaviors, leading to relapse.
Involved brain regions:
o Ventral tegmental area (VTA):
“Tells” other brain centers how rewarding an activity is.
VTA-neurons communicate by dispatching dopamine from the axon-
terminals to receptor-neurons on nucleus accumbens.
o Drugs cause a higher sensitivity to dopamine in the nucleus
accumbens.
o Animals with lesions in VTA or nucleus accumbens show no interest
in drugs.
All the regions talk to the reward pathway by releasing glutamate.
o Changes in the sensitivity to glutamate in the reward
pathway enhance both the release of dopamine from the
VTA and responsiveness to dopamine in the nucleus
accumbens " promoting CREB- and delta FosB-activity, and
the unpleasant effects of these molecules.
o The glutamate-sensitivity also strengthens the neuronal
pathways that link memories of drug-taking experiences
with high reward " desire to drug-seeking.
o Striatum:
Forming habits; routines of behavior we do without thinking.
Processing reward.
o Amygdala:
Helps to determine whether an experience is pleasurable or aversive
Determines whether the behavior should be repeated
, Creates connections between an experience and other cues
Emotion regulation
o Hippocampus:
Forming memories and learn of an experience (incl. where, when, with who)
o Frontal cortex:
Coordinate and process all this information and determine the ultimate
behavior.
Chronic/repeated drug-use causes changes in the structure and function of the reward system,
causing lower pleasurable effects, increased cravings, tolerance, and dependence.
Tolerance and dependence occur because frequent drug use can suppress parts of the
brain’s reward circuit.
o CREB (cAMP response element-binding protein) is a transcription factor; regulates
the expression/activity of genes, and thus neuron-behavior
cAMP gets active because of the dopamine in the nucleus accumbens, which in
turn activates CREB. After CREB is turned-on it binds to a specific set of genes,
triggering production of the proteins the genes encode.
Chronic drug use causes sustained activation of CREB, which enhances
expression of its target genes, some of which code for proteins that inhibit
the reward circuitry " causing tolerance by making the same-old dose of
drugs less rewarding.
CREB is switched off in days after drug-use stops, and thus can’t account for
long-lasting drug abuse.
Relapse is driven by sensitization = reinforcement of the drug-effect.
o Sensitization is caused by delta FosB (transcription factor).
Delta FosB concentrations rise gradually and
progressively in the nucleus accumbens.
It remains active in these neurons for weeks to
months after drug-administration, causing
hypersensitivity to drugs.
o Sensitization is also caused by sprouting of dendritic spines;
they support the cells’ connections to other neurons.
Delta FosB is responsible for the added spines
months after drug-use.
By the sprouting, there is heightened signaling "
overreaction to drug-related cues.
All drugs of abuse cause the nucleus accumbens to receive a flood of dopamine this explains why
all drugs can be addictive.
Case 3
Addiction is a brain disease
Problem statement: “?”
Learning goals:
I. How does the reward system work normally and within addiction?
II. What is the dopaminergic pathway of addiction?
III. What is the difference between a healthy and a drug addicted brain?
IV. What determines the maintenance of the addiction?
V. What neurobiological treatments are there for addiction?
BDMA: Brain Disease Model of Addiction " addictive behaviors change the brain in various ways,
which makes repeated relapse more likely, including changes in reward sensitivity, stress reactivity
and negative affect, and reduced cognitive control and self-regulation.
Addiction is a chronic disease.
How does the reward system work normally and within addiction? i
Chemicals in drugs boost the activity of the brain’s reward system ultimately.
A complex circuit of neurons which gives pleasure and encourages to repeat the activity.
o The reward by drug-stimulation is greater than any neutral reward.
The pathway extends from the dopamine-producing nerve cells (neurons) of the ventral
tegmental area (VTA) to dopamine-sensitive cells in the nucleus accumbens.
= The mesocorticolimbic dopamine system
o Stimulation of this pathway by cues reinforces drug-behaviors, leading to relapse.
Involved brain regions:
o Ventral tegmental area (VTA):
“Tells” other brain centers how rewarding an activity is.
VTA-neurons communicate by dispatching dopamine from the axon-
terminals to receptor-neurons on nucleus accumbens.
o Drugs cause a higher sensitivity to dopamine in the nucleus
accumbens.
o Animals with lesions in VTA or nucleus accumbens show no interest
in drugs.
All the regions talk to the reward pathway by releasing glutamate.
o Changes in the sensitivity to glutamate in the reward
pathway enhance both the release of dopamine from the
VTA and responsiveness to dopamine in the nucleus
accumbens " promoting CREB- and delta FosB-activity, and
the unpleasant effects of these molecules.
o The glutamate-sensitivity also strengthens the neuronal
pathways that link memories of drug-taking experiences
with high reward " desire to drug-seeking.
o Striatum:
Forming habits; routines of behavior we do without thinking.
Processing reward.
o Amygdala:
Helps to determine whether an experience is pleasurable or aversive
Determines whether the behavior should be repeated
, Creates connections between an experience and other cues
Emotion regulation
o Hippocampus:
Forming memories and learn of an experience (incl. where, when, with who)
o Frontal cortex:
Coordinate and process all this information and determine the ultimate
behavior.
Chronic/repeated drug-use causes changes in the structure and function of the reward system,
causing lower pleasurable effects, increased cravings, tolerance, and dependence.
Tolerance and dependence occur because frequent drug use can suppress parts of the
brain’s reward circuit.
o CREB (cAMP response element-binding protein) is a transcription factor; regulates
the expression/activity of genes, and thus neuron-behavior
cAMP gets active because of the dopamine in the nucleus accumbens, which in
turn activates CREB. After CREB is turned-on it binds to a specific set of genes,
triggering production of the proteins the genes encode.
Chronic drug use causes sustained activation of CREB, which enhances
expression of its target genes, some of which code for proteins that inhibit
the reward circuitry " causing tolerance by making the same-old dose of
drugs less rewarding.
CREB is switched off in days after drug-use stops, and thus can’t account for
long-lasting drug abuse.
Relapse is driven by sensitization = reinforcement of the drug-effect.
o Sensitization is caused by delta FosB (transcription factor).
Delta FosB concentrations rise gradually and
progressively in the nucleus accumbens.
It remains active in these neurons for weeks to
months after drug-administration, causing
hypersensitivity to drugs.
o Sensitization is also caused by sprouting of dendritic spines;
they support the cells’ connections to other neurons.
Delta FosB is responsible for the added spines
months after drug-use.
By the sprouting, there is heightened signaling "
overreaction to drug-related cues.
All drugs of abuse cause the nucleus accumbens to receive a flood of dopamine this explains why
all drugs can be addictive.
