Week 3 - E - Neurobiology of addiction - Diagnosing addiction, mesolimbic dopaminergic pathway - reward, stress effect on addiction

Question 1

What is the ICD-10 criteria for dependence? There are 6 parts to the criteria

Answer 1

* A strong desire to take the substance

* Difficulties in controlling substance use

* A physiological withdrawal state

* Tolerance

* Neglect of alternative pleasurs

* Persistence despite evidence of harm

Question 2

What acronym is used for diagnosing addiction? What do the letters stand for?

Answer 2

This acronym would be cage

C- cut down

A - annoyed

G - guilty

E - eye opener

Question 3

In the acronym C(cut down) A(annoyed) G(guilty) E(eye opener) for diagnosing addiction, what would be relevant for each section?

Answer 3

* Cut down - have you ever felt you eg drink too much and should cut down

* Annoyed - have people annoyed you by criticizing your eg drinking?

* Guilty - have you ever felt guilty about your addiciton

* Eye opener - have you ever needed to do the addiction to get to sleep or to get up in the morning

Question 4

When you experience a rewarding stimulus, what occurs in the brain?

Answer 4

When there is a rewarding stimulus, information travels form the ventral tegmental area and travels through the nucleus accumbens to the prefrontal cortex

Question 5

Which pathway is involved in normal pleasurable experiences? Which neurotransmitter is involved? It is often referred to as the reward pathway

Answer 5

This would be the mesolimbic pathway which acts with dopamine as its main neurotransmitter

Question 6

What does the mesolimbic pathway connect? Where in this pathway is dopamine released from?

Answer 6

The mesolimbic pathway connect the ventral tegmental area to the nucleus accumbens and olfactory tubercle which are located in the ventral striatium

It is the release of dopamine from the ventral tegmental area which starts the reward pathway

Question 7

Where is the ventral tegemental area located? What effects does the mesolimbic pathway have on behaviour?

Answer 7

The ventral tegmental area is located in the midbrain - just beside the substantia nigra

The mesolimbic pathway has the effect of incentive on behaviour - ie because this pathway causes reward, you will want to do it again hence the incentive - basically a motivation signal

Question 8

The dopaminergic activity in the mesolimbin pathway is involved in normal pleasurable activities as well such as eating food and sex What effects do drugs such as opioid, cocaine, amphetamine have on the mesolimbic pathway dopamine release?

Answer 8

These drugs majorly increase the release of dopamine as well when taken - hence why people can become addicted, addicted to the reward

Question 9

Can you develop a tolerance to reward?

Answer 9

Yes you can develop a tolerance to reward

Question 10

fMRI studies gambling addicts vs non-addicted controls Non- addicted controls had increased blood flow to the striatum upon winning Gambling addicts had significantly less response This suggests a tolerance to reward develops What is fMRI? What is found in the striatum which is part of the mesolimbic dopamine pathway?

Answer 10

fMRI - this is a functional MRI - detects changes in the brain associated with blood flow

In the striatum is the nucleus acuumbens part of the mesolimbic pathway

Question 11

During addiction to a substance, how does tolerance develop? What does this mean for normal rewards?

Answer 11

During addiction, due to repeated dopamine release there is the down regulation of the dopamine receptors in the brain

This means that the threshold for rewards is increased and normal experiences will not evoke an adequate reward response

Question 12

When taking a drug, there is a difference between the reason for it known as positive and negative reinforcement What does positive and reinforcement actually mean?

Answer 12

In the initial stages of taking a drug, you are driven by reward to keep taking it because it feels great - this is positive reinforcement In the later stages, the rewards of taking taking the drug wear off and you need to take the drug again, eventually it becomes a thirst - negative reinforcement

Question 13

What is the role of the prefrontal cortex in addiction?

Answer 13

The prefrontal cortex will help intention guide behavior

It helps modulate the effects of the reward pathway

The prefontal cortex also sets goals and focuses attentions as well as making sound decisions

Keeps emotions and impulses under control to achieve long term goals.

Question 14

How does the frontal cortex mature? Which part of the cortex is the first to mature?

Answer 14

The cortical maturation begins in a back to front manner

The cortex matures starting at the primary motor cortex which is situated at the posterior apsect of he frontal lobe (precentral gyrus) and then spreads workng its way to the prefrontal cortex

Question 15

Do frontal lobe areas that mediate executive functioning, or limbic systems mature first? What is limbic system important in regulation of?

Answer 15

Frontal lobe systems that mediate executive functioning mature much later than the limbic systems

Limbic systems are involved very much in the emotional response

Question 16

What does dopamine release effect in the prefrontal cortex?

Answer 16

Dopamine release effects: The ability to update information in the prefrontal cortex

The ability to set new goals

The ability to avoid compulsive repetition of a behaviour

Question 17

The earlier the age the drug experimentation starts, the longer the relationship with drugs. True or false?

Answer 17

TRUE

Question 18

WHat is the difference between the striatums and the hippocampals role in addiction?

Answer 18

The striatum is largely involved in habit learning when it coms to addiciton

The hippocampus is largely involved in declarative learning - being able to declare things eg capital of a state

Question 19

Describe the orbitofrontal cortex in addiction?

Answer 19

Addicted have increased activity with OFC when presented with drug cues.

Hyperactivity of the orbitofrontal corrtex correlates with the craving of drugs

Question 20

PFC – prefrontal cortex; ACG – anterior cingulate gyrus; OFC – orbitofrontal cortex; SCC – subcallosal cortex; NAc – nucleus accumbens; VP – ventral pallidum; Hipp – hippocampus; Amyg – amygdala

How can stress affect addiction? (acute and chronic stress)

Answer 20

Acute stress triggers dopamine addiction

Rapid increase can cause the seeking of drugs in dependent individuals

Chronic stress can lead to dampening of dopaminergic activity due to down regulation of dopamine receptors

This down regulation affects the sensitivity to normal rewards

This encourages exposure to highly rewarding behaviours

Question 21

RECAP What pathway is involved in incentive salience? What does overstimulation of this pathway cause? What puts the brakes on the reward pathway? Which part of the forntal cortex develops first and which develops last? What part of the brain is dysfunctional in addicted people?

Answer 21

The reward pathway is involved in incentive salience - Incentive salience refers to the “wanting” or “desire” attribute given by the brain – specifically, by the nucleus accumbens shell – to a rewarding stimulus.

Overstimulation of the reward (mesolimbic) pathway cause down regulation of the dopaminergic activation to reward

Th prefrontal cortex puts the brakes on reward

The primary motor area of the forntal cortex develops first, the prefrontal cortex develops last

In addicted people, preforntal cortex is dysfunctional