Lecture 30 - Behavioural and Developmental Aspects of Dependence

Question 1

Describe dopaminergic projections in the reward pathways in the brain

What is the normal role of this system?

Answer 1

1. VTA (ventral tegmental area)
2. Nucleus accumbens
3. PFC (prefrontal cortex)

Normal role:

• Dopamine is released in response to the normal reward stimuli
  
  • Eating, drinking, sleeping, sex etc.
• This reward reinforces these behaviours, ensuring the survival of the species.

Question 2

Describe the release and interaction with receptors of dopamine

Answer 2

1. Dopamine released by dopaminergic neurons
2. Dopamine acts on dopamine receptors on the post-synaptic neuron in the nucleus accumbens

Question 3

What is the pharmacological action of cocaine?

What is the general action of cocaine?

Answer 3

• General action:
  
  • Hijacks the natural reward system in the brain
  • The brain thinks that the drug taking is a very important behaviour for survival, and so this behaviour is heavily reinforced
• Pharmacological action:
  
  • Cocaine binds and blocks dopamine transporter protein
  • Dopamine not recycled back into pre-synaptic neurons
  • Increased action of dopamine on its receptors, as it is in the synaptic cleft for longer

Question 4

Compare the action of the following drugs on the reward pathways in the brain:

• Heroin
• Alcohol
• Cannabis
• Cocaine

Answer 4

Heroin:

• Converts to morphine in the body
• Acts on endogenous opioid receptors on GABA interneurons, inhibiting them
• VTA neurons become disinhibited by GABA interneurons
• Activates descending pathways of analgesia

Cannabis:

• CB binds CB R on GABA interneurons
  
  • ​GABA interneurons usually inhibit the dopaminergic neurons in the VTA
• Disinhibition of the dopaminergic neurons in the VTA
• Projection of the neurons to the nucleus accumbens

Alcohol:

Cocaine:

• Blocks re-uptake of dopamine in the nucleus accumbens

Question 5

Give the DSM IV definitino of substance dependence

Answer 5

“Maladaptive pattern of use, leading to clinically significant impairment or distress, manifested by at least 3 of the following in a 12 month period:

• Tolerance
• Withdrawal
• Substance taken in greater doses / longer than intended
• *Persistent desire *
• Unsuccessful efforts to decrease or control substance use
• etc.”

Question 6

Characterise patterns of heroin relapse

Answer 6

Physiological dependence is much easier to deal with than psychological dependence.

Relapse rates are significant, even after successful detoxification

• 42% use within days of leaving detox
• 66% readdicted 6 mths later
• After 7 years:
  
  • 48% still using
  • 12% dead
  • 5% in prison

Question 7

What factors need to be taken into account in understanding addiction?

Answer 7

• Intense cravings
• Loss over control of use
• Compulsive patterns of behaviour
• High rates of relapse

Question 8

Compare the effect of various drugs on the dopaminergic systems in brains of drug users, and non-drug users

Answer 8

Drug users:

• Decreased effect of reward stimuli
• Measured with MRI imaging of dopaminergic system

Question 9

What features are similar across all drugs of abuse?

What differs?

Answer 9

• All drugs of abuse increase dopamine in the reward systems
• However, they perform this action in different ways

Question 10

Why do people take drugs?

Why do people continue to take drugs?

Answer 10

• To feel good
  
  • ​Drugs release neurotransmitters in the pleasure centres
  • This does not explain why people continue to take drugs:
    
    • ​In the long term, the drugs do not have the same effect
    • In addition, there are many adverse outcomes associated with taking the drug
• Continuing use:
  
  • ​*

Question 11

Compare physiological and psychological dependence

Answer 11

• Physiological:
  
  • Experience
    
    • ​Tolerance
    • Withdrawal
  • This can happen to anyone that takes the drug for long enough
  • The individual does not feel a drive to continue taking the drug
• Psychological:
  
  • ​Individual actively seeks out the drug
  • Drug taken in larger doses
  • Continue the behaviour, despite the knowledge of the negative effects
  • etc.

Question 12

Define tolerance

Answer 12

• Increasing doses required to elicit the same response

Question 13

Define withdrawal

Answer 13

• When drug is taken away, strong unpleasant feelings
• The symptoms of withdrawal are the opposite of the effect of the drug
  
  • Depressants → stimulation in withdrawal
  • Stimulants → fatigue and lethargy in withdrawal

Question 14

Describe the role of environment in addiction

Answer 14

• Environmental cues can play a role in conditioning of reward
• The cue can act as a secondary reinforcer
  
  • ​In the absence of the primary reward, the individual will perform the behaviour in order to get the secondary cue
• Once detoxed, exposure to the cue will predict relapse, as well as withdrawal symptoms

Question 15

Describe hedonic allostasis

Answer 15

• A system can not be continually activated by stimuli
• eg Night out
  
  • ​An individual spends the night out, having a really good time; mood is elevated
  • The next day, the person feels flat, as the neurotransmitters are depleted
• The reward set point of the system changes
  
  • ​It becomes harder and harder to elicit the release of dopamine by the system, and thus to get the same high
• With drug use:
  
  • ​Once a person is taking drugs, natural highs don’t come close to activating the system, as the set point is now so elevated

Question 16

Describe Anhedonia in drug users

How was this researched experimentally?

Answer 16

• Drug users do not derive pleasure from natural reward stimuli
• Experimental design
  
  • ​Non-/Drug users were exposed to a range of images
    
    • ​Positive reinforcers
    • Negative
      
      • ​Snakes, drug use
  • Responses were recorded in a number of ways:
    
    • ​Reporting of how they felt
    • Facial expression
    • Cortical activity
• Results:
  
  • ​For every parameter, heroin users were overreactive to the opiate images and under-reactive to the natural reinforcers

Question 17

Which brain regions are altered in drug users?

What is the function of these regions?

Answer 17

• Regions
  
  • Orbitofrontal cortex
    
    • ​Making long term goals
    • Weighing up short vs. long term goals
  • Anterior cingulate cortex
    
    • ​Keeping one on track with goals and plans

Experimental studies:

• Two groups:
  
  • ​Drug naïve
  • Drug users
• Perform various tests
  
  • ​Wisconsin card sorting test
    
    • ​Test of executive function
    • No difference between the groups
  • Gambling test
    
    • ​Two decks
      
      • ​Advantageous
      • Disadvantageous
    • Drug users and those with OFC lesions consistently select from the disadvantageous deck, and ultimately lose all their money

Question 18

Which comes first: the brain deficits, or the addiction?

Answer 18

• NB brain deficits:
  
  • Decreased activity of OFC and ACC
• It is unclear which comes first
  
  • ​Chicken and the egg scenario
• Experimental studies have indicated that the deficits can be pre-morbid
  
  • ​Smaller OFC in kids age 12 that go on to use cannabis at age 16, compared to those who don’t
  • Poorer response on brain function tests measuring function of these areas in kids with a strong family history of alcohol, than those with no family history
    
    • ​These kids have never had alcohol

Question 19

Describe Anhedonia in adolescents

What is thought to be the evolutionary basis for this?

What are the implications?

Answer 19

• Increased anhedonia in adolscents
  
  • Compared to younger or older individuals
  • Increased ‘boredom’
  • Experience positive experiences as less pleasurable than others
• Evolutionary basis
  
  • During adolescence, one must learn to look after oneself, gain new experiences, risk take etc.
  • Anhedonia could perhaps lead adolescents to seek these new experiences
• Implications:
  
  • Adolescents are more at risk of addictive behaviours?

Question 21

Describe the developmental changes that occur in the brain over time

Answer 21

Childhood:

• Massive proliferation of connections

Adolescence:

• ‘Pruning’ : removing the connections that aren’t needed
• Myelination: insulation of the important connections
• This doesn’t happen in an ordered way
  
  • Certain areas develop faster than others
    
    • ​Limbic system develops first
      
      • ​Region that tells individual to go out and try new things
    • PFC develops later
      
      • ​By age 25
      • Region that is important for judgements and control of behaviour

Question 22

Outline the studies into alcohol intake in adolescent and adult rats

Answer 22

• ‘Rat bar’ experiment
• Rats able to consume alcohol at will / intermittently
• Adult rats consume less alcohol than adolescent rats
• When alocohol consumption is restricted, adolescent rats drink more alcohol per day
  
  • ​⇒ more likely to binge drink

Question 23

Compare the effect of alcohol on adult and adolescent rats

Answer 23

• Adults
  
  • ​Motor control more affected than adolescent rats
• Adolescents:
  
  • ​Suffer less from the immediate physical effects (such as motor impairment)
  • However, brains are more vulnerable to damage
    
    • ​Memory and learning functional impairment
  • Suffer more frequently from black outs

Question 24

Describe studies into hippocampal size in the brain of adolescents who consume large amounts of alcohol

Answer 24

• Hippocampus size is reduced in alcohol dependent adolescents
• Size of hippocampus is inversely proportional to the amount of alcohol consumed

Question 25

Describe the addictive features of nicotine

Answer 25

• Adult rats will not hit a lever in order to receive nicotine
• Unless they are previously injected and thus dependent
• In contrast, adolescents love nicotine
  
  • ​esp. females
• This is linked to depression

Question 26

Which age group is most at risk of the harms of alcohol?

Answer 26

Adolescents