Basic science of Substance Abuse

Question 1

What are the 2 distinct mechanisms involved in substance misuse?

Answer 1

• Tolerance
• Reward centre

Question 2

What forms the basis of pyschologcial cravings for a substance like alcohol / drugs etc?

Answer 2

The reward centre

Question 3

What forms the basis of the physical dependence on a substance?

Answer 3

Tolerance

Question 4

How do you define tolerance?

Answer 4

Reduced responsiveness to a drug caused by previous administration

Question 5

Which types of drugs can you develop a tolerance to?

Answer 5

Opioids, ethanol, barbiturates, benzodiazepines

Question 6

What are the 2 key Mechanisms of Tolerance?

Answer 6

• Dispositional tolerance
• Pharmacodynamic tolerance

Question 7

Describe what Dispositional tolerance is? and give 3 possible reasons for this

Answer 7

Dispositional tolerance is when less drug reaches its site of action - doesn’t get to the receptor

• Less drug absorbed i.e from the gut
• Drug metabolised faster
• More drug excreted

Question 8

Describe what pharmacodynamic tolerance is? and give 2 possible reasons for this

Answer 8

Less action at the active site i.e when it binds to the receptor, it doesn’t have as much of an effect

• Fewer drug receptors (the receptors are internalised or down-regulated)
• Less efficient drug receptors – reduced signalling down stream so less secondary messengers etc

Question 9

What happens when the neurones in the ventral tegmental area are stimulated?

Answer 9

Dopamine is released

Question 10

What does a release of dopamine do to us as humans?

Answer 10

It gives us a sensation of pleasure / reward

Question 11

What is the reward pathway normally activated by? And why has it evolved?

Answer 11

• Eating, drinking and sex
• It therefore encourages those “healthy” behaviours that lead to propagation of your genes

See the ventral tegmental area (VTA), the nucleus accumbens (nuc. acc.) and the prefrontal cortex and the pathway connecting these structures. The information travels from the VTA to the nucleus accumbens and then up to the prefrontal cortex. This pathway is activated by a rewarding stimulus. (It is not the only pathway activated by reward, other structures are involved too, but only this part of the pathway is shown for simplicity)

Question 12

How do the following common drugs tap into the reward pathway?

1. Heroin
2. Cocaine
3. Amphetamine

Answer 12

1. Heroin increases firing rate of dopaminergic neurones
2. Cocaine inhibits dopamine uptake
3. Amphetamine increases dopamine release

This produces the psychological component of addiction - “craving”

Question 13

Give 2 reasons why it is important that substances which artificially stimulate your reward pathway should be made illegal/have guidance around them?

Answer 13

• Societal reasons – as these substances can make people engage in illegal activities
• Dismotivation from people because if they get the dopamine release from drugs all the time they don’t need to get it from normal things like eating, drinking and sex

Question 14

Is there such a thing as an ‘addictive personality’ i.e do genetics play a role in addiction?

Answer 14

Yes, for example the A1 allele of the D2 dopamine receptor gene is linked with severe alcoholism

Your genetic make has an effect on your reward pathway and therefore their craving is stronger

Question 15

Look

Answer 15

See notes for mechanism of tolerance and dependence