2) Reward System + Substance Abuse

Question 1

How is alcohol use disorder diagnosed (using DSM-V)?

Answer 1

Alcohol consumption can be described on a continuum:
social use → risky drinking → alcohol use disorder (mild, moderate, severe)

The severity of alcohol use disorder depends on the number of diagnostic criteria met:
2-3 = mild
4-5 = moderate
6+ = severe

Diagnostic criteria:
1. Tolerance
2. Withdrawal
3. Cravings
4. Unsuccessful attempts to cut back
5. Using more than intended
6. Using despite negative effects (physical, psychological, social)
7. Failure to fulfill obligations (work, home, school)
8. Significant time spent (obtaining, using, recovering)
9. Giving up other activities (social, work-related, recreational)

Question 2

What is the pathogenetic model of alcohol dependence? What role does genetics play?

Answer 2

The pathogenetic model describes how the progression from
social use → risky drinking → abuse → dependence
is influenced by genetics, environment, and substance-related factors.

Genetic factors play a significant role (as demonstrated by twin studies).
* Alcohol dependence is polygenic, involving multiple genes. For example, a mutation in the D2 dopamine receptor (D2DR) is linked to reduced receptor density.
* Additionally, personality traits like impulsivity and sensation seeking may predispose individuals to alcohol dependence.

Question 3

Individuals with SUD (substance use disorder) usually cycle through various motivational stages. What are they?

Answer 3

Precontemplation (no intention of changing behavior)
Contemplation (aware a problem exists; no commitment to action)
Preparation (intent upon taking action)
Action (active modification of behavior)
Maintenance (sustained change, new behavior replaces old)
Relapse (fall back into old patterns of behavior)

Question 4

What are the central structures of the reward system? How do they interact?

Answer 4

The mesolimbic dopamine system includes:
* the ventral tegmental area (VTA)
* the nucleus accumbens (NAc)

The VTA releases dopamine on the NAc.
The NAc processes dopamine signals from the VTA.

The VTA is located in the midbrain.
The NAc is located in the ventral striatum of the basal ganglia.

Question 5

All addictive drugs trigger brief, intense bursts of extracellular dopamine in the NAc.

How do stimulants and nicotine trigger this dopamine increase, compared to drugs like opioids, alcohol, and PCP?

Answer 5

• Stimulants and nicotine directly increase dopamine release at the NAc.
• Opioids, alcohol, and PCP indirectly increase dopamine by suppressing inhibitory neurons that modulate the VTA+NAc.

Question 6

What is tonic dopamine firing vs. phasic dopamine firing?
What receptors and cognitive functions is each associated with?

Answer 6

Tonic dopamine firing = slow, low amplitude (sustained time course)
* D1 dopamine receptors (low affinity for dopamine)
* Modulates working memory + other cognitive functions

Phasic dopamine firing = fast, high amplitude (short bursts)
* D2 dopamine receptors (high affinity for dopamine)
* Reward system; induces substance “high” + conditioned responses (anticipation rather than actual reward perception)

Question 7

Chronic drug abuse induces persistent changes in the brain.

Clinical evidence of these changes includes:
* Tolerance, withdrawal
* Anhedonia when not using
* Persistence of cravings + risk of relapse after years
* Lower response to natural rewards

What are the neural correlates of these persistent changes?

Answer 7

Chronic drug abuse downregulates dopamine receptors + dopamine production.

High cravings correlate with the availability of dopamine receptors (especially D2 in the NAc), as well as of opiate receptors.

For example:

• Alcohol abuse causes the downregulation of D2 receptors (decrease in number/sensitivity) in areas like the NAc and the striatum, leading to drug tolerance and reduced pleasure from natural rewards.
• Detoxified alcoholics have an increased opioid receptor availability, possibly leading to increased cravings and sensitivity to cues.

Question 8

The dual systems model of addiction helps explain why psychotherapy has only moderate and transient effects on addictive disorders.

What are the two systems, and what cognitive processes do they influence?

Answer 8

The impulsive system = automatic processes (involves striatum, amygdala, vmPFC)
The reflexive system = cognitive control (involves insula, dlPFC)

Therapy is effective for the reflexive system, but not the impulsive system.
However, treatments like Bias Modification Training (e.g. the approach-avoidance task) can help address the impulsive system.

Question 9

Chronic drug use reduces sensitivity to non-drug reinforcers.

For example:
In the monetary incentive task, healthy individuals show normal brain activity in anticipation of monetary gain or loss.
Detoxified patients with alcohol dependence, on the other hand, show reduced activation in the ______.

Answer 9

ventral striatum (i.e. the nucleus accumbens)

This might help explain their decreased sensitivity to non-drug reinforcers, such as money.

Question 10

What determines the reinforcing potential, i.e. addictiveness, of a substance?
How does this relate to cravings, the “high” feeling, and addiction?

Answer 10

The reinforcing potential (i.e. addictiveness) of a drug depends on its fast uptake in the brain. This is because fast uptake results in fast dopamine release.

Bursts of dopamine correlate with cravings and the “high” feeling.
They are necessary (but not alone sufficient) for the development of addiction.

Question 11

Dopamine is not the only neurotransmitter involved in substance use and addiction. What other neurotransmitter systems does alcohol involve?

Answer 11

• GABA receptors (alcohol is a powerful GABA agonist)
• Opioid receptors
• Glutamate (NMDA) receptors
• Serotonin
• Norepinephrine