1. UW Bio Unit 1 Lecture 6
The Addicted Brain

2. Learning Targets & Success Criteria for Lecture 6
I can explain the changes that occur in the brain of an addict
Success Criteria
understand neuronal substructure in the context of the reward pathway
Describe the role of other neurotransmitters into the addiction story
Identify brain structures involved in the addiction story
understand addiction from a perspective of timeline
understand the hallmarks of addiction and decide if a new compound is addictive based on these hallmarks
learn about relapse and options for enabling withdrawal and preventing relapse

3. Pre-Test Which of the following are excitatory neurotransmitters?
Dopamine
GABA
Glutamate
In the reward pathway, where are dopamine recycling transporters?
In the ventral tegmental area on the dendrites
In the ventral tegmental area on synaptic bulbs
In the prefrontal cortex on the dendrites
In the nucleus accumbens on the dendrites
In the nucleus accumbens on synaptic bulbs

4. Pre-Test What is the job of the amygdala?
To help us understand and react to sensory stimuli
To help us understand and react to emotions
To help us make decisions and learn computational skills
To help us keep our bodies in homeostasis
To help us keep ourselves coordinated and balanced

5. Dopamine: The Risk to Use
It takes guts to decide to do something that others think is addictive….
It’is a gamble to get started on an activity that leads other’s down the road to addiction.
People who tend to want to TAKE that gamble are risk-takers and adventure seekers.
We are all comfortable with different amounts of novelty in our lives. .
Are you a risk-taker? A thrill-seeker?
Or are you a homebody – easily satisfied?
It takes guts to decide to do something that others think is addictive….
Potential consequences??
Don’t believe the hype of your peers testimony ??
Addicted people are just weak??
Whatever the reason, it is a gamble to get started on an activity that leads other’s down the road to addiction.
People who tend to want to TAKE that gamble are risk-takers and adventure seekers.
We are all comfortable with different amounts of novelty in our lives.
Some of us are home bodies, enjoying a good book in front of the fire.
Others are novelty-seekers, always looking for the next thrill, jumping in the car when a friend comes by to go bungee jumping.

6. Dopamine: A Partial Story
Why Risk Taking?
The key is how dopamine is received in the nucleus accumbens
Lots of factors influence this complex trait of being a thrill seeker
crave excitement partially because our dopamine reward system is “hungry”.
Dopamine receptors are proteins encoded by the corresponding gene
Different versions of that gene will give rise to different versions of the receptor  some bind dopamine well and others do not.
Image citation
NIDA -

7. Dopamine: Reward Deficiency Syndrome
These different versions of the dopamine receptor are linked with a phenomena termed the Reward Deficiency Syndrome (RDS).
PET scans that show people who have addictive disorders and others without
Shows available dopamine receptors in bright colors, red and yellow.
low high
Available dopamine receptors

8. Dopamine: Reward Deficiency Syndrome
There are more available dopamine receptors in people who are not addicts
so a little dopamine will go a long way and be very satisfying
Individuals that have a reduced ability to to respond to dopamine will crave opportunities that increase their chances of getting SOME dopamine stimulation risk takers
low high
Available dopamine receptors

9. Glutamate: The Frontal Lobes Talk Back
Stimulating the nucleus accumbens (NA) produces euphoria when drug- using is new
continued use reduces this euphoric sensation
Many people continue to use the drug partly because the circuitry of the brain is not one-way
dopamine
glutamate
Image citation
NIDA -
The neurons that communicate from prefrontal cortex (PFC) to the nucleus accumbens (NA) utilize the excitatory neurotransmitter  glutamate.

10. Glutamate: The Frontal Lobes Talk Back
Prefrontal cortex (PFC) receives a message from the NA sends messages back
reinforce the behavior that led to the release of dopamine initially.
Feedback from the PFC says “Got the message and I liked it!
Strengthens this pathway”… “I want more”
dopamine
glutamate
Image citation
NIDA -
The neurons that communicate from prefrontal cortex to the nucleus accumbens utilize the very common excitatory neurotransmitter  glutamate.

11. Glutamate: The Frontal Lobes Talk Back
occur partly because of strengthening synaptic connections
More synapses between two cells or refining the fine structure of those synapses.
This is part of why a user continues to use
dopamine
glutamate
Image citation
NIDA -
The neurons that communicate from prefrontal cortex to the nucleus accumbens utilize the excitatory neurotransmitter  glutamate.

12. Learning to Use Drugs Cognitive learning- Psychomotor learning
Recall previous decisions made and associated responses
Psychomotor learning
The user recalls the physical processes associated with using the drug.
This makes it easier to perform these activities later.
Affective learning
the user remembers the pleasure experienced while using the drug and seeks to relive that experience.
Image citation
“memories” by artist Frederick Leighton – public domain
What are the brain areas involved in learning and memory?

13. Biochemistry of Learning
The glutamate projections from the PFC don’t just go back to the NA to reinforce the pathway.
They also go to several areas of the brain responsible for cognitive, psychomotor, and affective learning.
Part of the thalamus is associated with recall and associative memory (making connections between cause and effect).
Glutamate neurons from the PFC arrive at the thalamus are involved in cognitive memory.
The amygdala is associated with emotional learning. (affective memory).
The ventral pallidum communicates with motor cortex.
so projections from the PFC to the ventral pallidum are thought to reinforce psychomotor memory formation.

14. Biochemistry of Learning
hippocampus
thalamus
Prefrontal
cortex
amygdala
ventral
pallidum
Ventral
tegmental
area
Nucleus
accumbens
dopamine
glutamate

15. Biochemistry of Learning
Drugs of abuse bind to the areas already described but many of them don’t influence dopamine or glutamate direction.
another neurotransmitter that is important in continued use of a drug, other than dopamine & glutamate GABA.
GABA’s role is largely to keep the pathway under control acts as the traffic cop
GABA is inhibitory and helps to prevent the firing of dopamine and glutamate neurons.
Therefore when GABA is inhibited, the regulation is weakened

16. Biochemistry of Learning
hippocampus
Thalamus
Prefrontal
cortex
amygdala
ventral
pallidum
Ventral
tegmental
area
Nucleus
accumbens
dopamine
glutamate
GABA 16

17. Craving and Relapse
Dopamine and serotonin are important neurotransmitters in determining who will start using an addictive substance.
Dopamine, glutamate, and GABA are important biochemicals that drive users to continue using addictive substances.

18. Craving and Relapse
Many people successfully quit using an addictive substance.
sheer will power
medication
“once an alcoholic [for instance] – always an alcoholic”.
The notion here is that even when not engaged in drinking, an alcoholic is a person who can easily become addicted to alcohol.
A past user is enticed back into drug use in ways that involved drug-learning just discussed and to be further considered in activity 6.

19. Recap on the Biochemistry of Addiction
Dopamine signals influence why people seek drug use and why drug use can feel good.
Glutamate signals reinforce feel-good circuits and stimulate learning about the drug related experience on three levels of memory.
GABA signals help to keep these pathways regulated.
Image citation
Brain areas responsible for addiction – NIH – public domain:

20. Addiction Stages
Initiation = initial exposure – do you WANT to try something that might be dangerous or illegal or at least merely self-gratifying?
Continuation = continued use – do you keep using something despite it being “frowned upon” by law or friends or family?
Cessation= stopping – can you stop using that thing when you choose to? Or do you continue to use it despite severe harm to self or others?
Relapse = after you do succeed in quitting, can you stay “clean”? How difficult is it to fight the urges? What triggers those urges?

21. Addiction – the “stages”
Decision to use (or not)
dopamine
Decision to REuse
GLUTAMATe
Compulsive use
Regulates emotional learning
Regulates (reduces) fear avoidance
Decision to withdrawal
Decision to use – are we wanting novelty? Are we feeling need for mood elevation? Are we inspired by others, by cues, by glamour of drug use?
Decision to REuse – was the first experience pleasurable?
Addictive use – has using become an obsession? Do we crave drug? Do we ignore other needs to use drug?
GLUTAMATe
Relapse
Heightened response to little cues
Hard to ignore desire to use again

22. Addiction’s Hallmarks
A drug that qualifies on all “hallmarks of Addiction” is very likely to be an addictive drug.
The drug stimulates the Reward pathway
The use of the drug leads to Tolerance
The use of the drug leads to Dependence, making it hard to Withdraw from drug use

23. Treatment Options 3- Pharmaceuticals
Drugs being developed and tried to replace the reward pathway stimulation that is lost when one quits using a euphoria-inducing drug.
1-Drug treatment programs exist to help people conquer their addictions
include behavioral or cognitive therapy as well as drug therapy
2- Substitution Therapy
Nicotine users may try a nicotine patch or gum
Heroin addicts may try methadone in place of heroin to reduce withdrawal symptoms
Trade one addiction for another

24. Relapse Happens
People who make great progress in breaking free of addiction can, with relatively minor prompting, get right back in to their old ways.
ing8.html

25. ER6 Required: Liska- Section of Drug Dependence & Addiction -1.7
Internet
addiction_22.html
substance-abuse-which-came-first_54.html
 Supplemental
Scientific American – Hallucinogens as Medicine (this will be required reading in Unit 6)
medicine