UW Bio Unit 1 Lecture 6 The Addicted Brain

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

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

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

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.

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 - http://www.drugabuse.gov/pubs/teaching/Teaching2/largegifs/slide11.gif

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

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

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 - http://www.drugabuse.gov/pubs/teaching/Teaching2/largegifs/slide11.gif The neurons that communicate from prefrontal cortex (PFC) to the nucleus accumbens (NA) utilize the excitatory neurotransmitter  glutamate.

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 - http://www.drugabuse.gov/pubs/teaching/Teaching2/largegifs/slide11.gif The neurons that communicate from prefrontal cortex to the nucleus accumbens utilize the very common excitatory neurotransmitter  glutamate.

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 - http://www.drugabuse.gov/pubs/teaching/Teaching2/largegifs/slide11.gif The neurons that communicate from prefrontal cortex to the nucleus accumbens utilize the excitatory neurotransmitter  glutamate.

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 http://commons.wikimedia.org/wiki/File:Frederick_Leighton_-_Memories.jpg What are the brain areas involved in learning and memory?

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.

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

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

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

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.

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.

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: http://upload.wikimedia.org/wikipedia/commons/5/51/Dopamine_Pathways.png

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?

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

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

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

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. http://www.drugabuse.gov/pubs/teaching/teaching6/Teach ing8.html

ER6 Required: Liska- Section of Drug Dependence & Addiction -1.7 Internet http://www.addictionsearch.com/treatment_blog/stages-of- addiction_22.html http://www.addictionsearch.com/treatment_blog/depression-or- substance-abuse-which-came-first_54.html http://www.drugabuse.gov/scienceofaddiction/addiction.html http://www.drugabuse.gov/scienceofaddiction/treatment.html  Supplemental Scientific American – Hallucinogens as Medicine (this will be required reading in Unit 6) http://www.scientificamerican.com/article.cfm?id=hallucinogens-as- medicine