Drug Addiction 2 Flashcards
What’s an assay for addictive potential in humans?
Drug self administration Usually IV pump works for all except alcohol-(cause rats avoid this) Does'nt work for non addictive drugs - FR
What is an FR schedule? What does it cause at different doses? Why is it difficult to interpret?
Fixed ratio: # presses to get a reward.
Get a typical dose response curve, inverted U shape.
- higher doses the number of presses declines cause of satiation, aversive reactions or side effects, or physically unable to press
- manipulations are difficult to interpret cause increased pressing could mean that 1) increased liking or wanting 2) compensatory casue you reduced rewarding effets of the drug so they’re pressing more
What happens when a new drug comes out and you wana see if its okay to give to public?
Do a FR schedule to see if they self administer.
What is PR schedule?
Progressive ratio schedule. # of presses incresaes.
Measuring breakpoint.
Measuring motivation to obtain drug.
At optimal doses of drug, animals will work super hard to get it. (harder than lower or too high doses)
What happens when you deplete dopmaine in NAc
INITIAL LERNING. Abolishes the learning in all but opiates (cause they are reinforcing on their own)
TRAINED TO SELF ADMINISTER
- on FR schedule, DA antagonists increase lever pressing.
- on PR schedule, breakpoint decreases. Reduced motivation for the drug.
How do you measure the rewarding effects of a drug?
Conditioned place preference (two places that make a learned association) - no lever pressing
- gets drug either way.
- just a measure of how much it likes it.
At high doses, you get place AVERSION.
Drugs of abuse get this place preference when given systemically or right into the NAc.
What happens to place preference when you block DA receptors in NAc?
Blocks place preference.
- also dependent on the amygdala, if you block that it doesn’t work
Which addictive drugs induce place preference?
all of them
describe the conditioned place preference in humans.
Find a ball, then get a reward at the same time shown a background. OR another ball and get nothing. At the end of experiment, asked which background they like more
1) healthy people like the rewarded background more
2) parkinsonian patients did not show a preference.
NO ASSOCIATION about the reward: means that you have things in your life that you probably don’t know why you like.
DEPENDANT ON DA TRANSMISSION.
Describe DA sensitiztion.
Repeated exposure to ALL addictive drugs cause sensitization to DA transmission. (same dose of drug causes a lot of increase)
- hyperdopamine state. (even after 4 days, can stay for a year in humans)
INCREASED MOTIVATION to seek drugs in response to cues.
How do you model drug relapse?
Reinstatement paridigm.
- rat given cues and a drug, lever presses measured
- rat then in extinction, lever presses go down.
- rat given a trigger, then drug seeking behavior REINSTATED-more lever presses (even tho they aren’t getting any drug) with triggers by giving either cue, stress or a little bit of the drug (itty bitty)
FOUND
1) DA release in NAc increases in response to the trigger, and
2) lever pressing increases almost back to step 1)
What happens to reinstatement when you block DA receptors in NAc?
Reduces/Abolishes reinstatement in ALL DRUGS.
- DA antagonists block Cue and stress induced reinstatement
MEANING: ability of triggers to reinstate drug seeking is dependent on DA transmission
What are the neural circuits that underlie drug relapse (reinstatement).
DA system circuits
PFC, NAc, Amygdala
- inactivating DA in these areas reduces reinstatement.
Repeated drug exposure can make these areas more responsive to “triggers”
In humans: PET studies have been shown that when you give them triggers, these brain regions activate and they say they are craving more.
Summarize dopamine’s effect on addiciton.
- Addictive drugs increase mesolimibic DA levels (not liking, but wanting)
- when drugs induce DA release, they make your brain think something important is going on and brain makes associations with environmental cues linked to drug taking
3) reward associated cues increase DA release in NAc, can trigger same behaviors (drug seeking)
4) drug use sensitizes the DA system that may amplify effects of cues
Describe the Incentive sensitization hypothesis
- cues take control over behavior.
Hedonic effects: tolerance (liking decreases)
Dopamine and drug related cues: sensitized (wanting increases)
Multiple cues can activate the DA system to trigger conditioned responses : cravings.
- make you THINK you WANT the drug (similar to how food makes you hungry)
These effects are amplified by the hyperdopamineric state.
- positive feedback loop even if the drug isn’t pleasurable.
