Lecture 31: The Neurobiology of Addiction Flashcards
What are the annual deaths from tobacco? Alcohol? Cocaine + heroine?
450,000
100,000
5000 + 2000
What is diaphoresis?
Excessive sweating commonly associated with shock and other medical emergency conditions
What do you do if your colleagues are abusing drugs or alcohol?
Get them into treatment because they do the best with treatment
Is environment important for addiction?
Not really
Example: babies in Scandinavia who had alcoholic parents who were adopted into a nonalcoholic family had the same prevalence of alcoholism as did babies who had alcoholic parents and were raised in an alcoholic household
Genes are most important…
What is the most important factor in determining your susceptibility to addiction?
Genetics, heritability
Certain people are more genetically predisposed to addiction than others
What is the definition of addiction?
When you do something that is harmful but you CANT CONTROL IT
Drug use that is “out of control”
Disorder of reward system
-compulsive use
What is the difference between dependence and addiction?
Dependence = NORMAL response … such as dependence on caffeine to stay awake (withdrawal symptoms)…also pain medication and gaining tolerance Addiction = you literally cannot stop
Is tolerance and withdrawal symptoms of addiction if the drug is prescribed?
No, if physicians prescribe shit to you, tolerance/withdrawal are normal
Which drug has the highest rate of addiction among those who try it?
Nicotine
31.9% of people who try cigs get addicted
vs.
16.7% of people who try cocaine get addicted
What are the key areas of reward system?
Dopaminergic release into the nucleus accumbens
What drugs increase dopamine in nucleus accumbens?
- Nicotine
- Cocaine
- Alcohol
- Opiates
What is compulsion?
An irresistible impulse to act regardless of the rationality of the motivation
-a strong irrational impulse to carry out a given act
What is the prime target of addictive drugs?
The mesolimbic dopamine system
What is the mesolimbic dopamine system?
Originates in the ventral tegmental area (the middle part of the midbrain…remember the cross sections and how tectum was the roof)
-projects to the nucleus accumbens, the amygdala and the hippocampus and the prefrontal cortex
What neurotransmitter is released by neurons of VTA?
Dopamine
How does the mesolimibic dopamine (ML-DA) sytem work? Significance?
When VTA begins to fire, large quantities of dopamine are released into the nucleus accumbuns and the prefrontal cortex
-this leads to strong reinforcement
Drugs of abuse are dopaminergic in that it leads to this constant reinforcement of action…
-mesolimbic dopamine codes for the DIFFERENCE between expected and actual reward and leads to a strong learning signal
What are the three classes of addictive drugs?
1. drugs that bind to GPCR Can bind to Gi and leads to LESS inhibition from GABA so more dopamine signals Examples: i. opioids ii. Cannabinoids iii. Gamma-hydroxybutyric acid (GHB) iv. LSD, mescalin, psilocybin 2. drug that interacts with inotropic receptors (ion channels) Can allow for more dopamine to go through channels Examples: i. nicotine ii. alcohol iii. benzodiazepines iv. phencyclidine, ketamine
- drug that targets the dopamine transporter
Can inhibit dopamine reuptake channels and thus increases the duration of dopamine in the synapse
Examples:
i. Cocaine
ii. Amphetamine
iii. Ecstasy
What are the only non-substance addictions?
Gambling
Computer games
What are the three variables that interact to lead to addiction?
- Agent
- Host
- Environment
What influences the agent variable for addiction?
Availability of drug
- dose of drug
- price of drug, leads to tendency to try drug
What influences the host variable for addiction?
Heredity
- inherit tolerance
- metabolism of nicotine/alcohol
- amount of reward
What influences the environment variable for addiction?
Role models
Stress
Boredom
Peer pressure
What is tolerance?
The phenomenon in which the dose of a drug needs to be increased in order to maintain the same effect
Patients can have addiction with NO tolerance
Innate vs. acquired
Can someone be addicted and NOT have tolerance?
Yes, tolerance is neither necessary nor sufficient for addiction
What is cross tolerance?
Treating withdrawal with a similar medication
Tapering off used for detox
Examples: methadone for heroine/opioids
-oxazepam for alcohol
What is sensitization?
Reverse of tolerance
Stimulants can have an increased effect with REPEATED and spaced dosing
What is the effect of cocaine, meth and alcohol on D2 receptors?
They SATURATE them because there is so much dopamine in the synapse, one way or another
What happens to people with more D2 receptors who are given methylphenidate? Someone with less D2 receptors?
They hate it
Less D2 receptors respond better to methylphenidate
What are the factors leading to relapse?
- Psychiatric problems like depression and anxiety
- Social problems
- unemployment
- family problems
- peer influence
- Conditioned Responses
Are “pure” addicts common or rare?
Rare
- most addicts have additional problems
- treatment depends on additional problems
- high treatment success for “pure” addicts
What areas of the brain are activated when someone is given a cue that induces CRAVING?
- Anterior cingulate
- Amygdala
The reward system
What is the takehome point for O’Brien’s Addiction lecture?
Addiction is a chronic brain disorder persisting long after every trace of the drug has left the body. An important component consists of reflex activation of reward circuits in response to drug cues
