Drug Addiction Flashcards
What is the putative definition for Drug addiction?
A chronic neuobiological disease
Define the addiction cycle and its 3 stages
Preoccupation anticipation (persistent desire, larger amounts taken than expected)
Binge intoxication (Tolerance withdrawal, compromised social/occupational/recreational activities)
Withdrawal/negative affect (Preoccupation with obtaining, persistent physical/psychological problems)
What was Heyman’s Hypothesis for drug addiction?
He views addiction as resulting from suboptimal everyday decision making
“Temporally myopic view of the available alternatives”
What are the 3 animal models of testing addiction learned in class?
Intracranial Self Stimulation (ICSS)
Intravenous Self Administration (IVSA)
Conditioned place preference (CPP)
Describe the procedure of ICSS testing
Mouse has a microdialysis array set up that releases drug when the rat presses a lever
Where does ICSS release the drug in the brain?
In the Nucleus Accumbens
Along with Ventral Tegmental Area, forms the Mesolimbic Dopamine System
How can ICSS test for a rat’s drug threshold?
Two levers in the testing box with rat
One lever provides the rat with decreasing amounts of drug, other lever resets dose
Can measure how far a rat will go before it decides the dose is too low and resets
What drug caused a decrease in rats’ threshold during ICSS? What does this imply?
d-Amphetamine
Exerts a reinforcer-enhancing effect (not saying amphetamine is more rewarding, just makes the brain more sensitive to rewards)
Describe the procedure of testing IVSA. Why are there two levers?
Infusion pump hooked up to lever, same as ICSS but instead of direct cranial stimulation the drug is introduced intravenously
Two levers to rule out random movement
Drug lever only active for 1-3 hours a day, hardly any withdrawal
What does the unit/dose per dose graph show?
Inverted parabola
Rats will continue to consume cocaine until they reach a target conc, then they try to stay there
(Rats will take fewer doses when the unit dose is higher)
Describe the results of IVSA testing with cocaine on rats given pimozide (a DA antagonist)
At low doses of pimozide, nothing unusual
At medial doses, increase in infusions (rat was willing to work harder for the same amt of drug)
At higher doses, rat just lost interest in pressing the lever
Describe the Progressive Radio reinforcement schedule for IVSA
Button press causes infusion, but the number of presses to reach infusion increase each time
Used to test at what point the rat gives up and decides it isn’t worth pursuing
Describe the results of PR testing on rats with varying levels of cocaine/dose
The rats were more determined at higher doses and were willing to go farther
Each unit dose conc showed a ‘post reinforcement pause’ after each dose where the rat had just been infused and stopped pressing the lever
Describe the testing procedures for Conditioned place preference (CPP)
Rat undergoes 3 stages in a box with two distinct wallpapers, scents, etc with a removable wall between them:
1 Habituation - No injection, just allowed to explore both sides
2 Condition - give drug in one box and saline in the other
3 Test day - Measure time on drug associated side
What were Dr. White’s results when testing CPP in rats with amphetamine in different locations of the brain?
Amphetamine only increased CPP when it was administered to the Nucleus Accumbens
What is an alternative method to CPP and what drawback is common to both?
Conditioned Place Aversion (CPA) where the rat would avoid the compartment where eg it experienced withdrawal
Both tests require that learning and memory are intact (not a pure test of reward)
Why is addiction complex?
Many factors go into it
What symptoms of withdrawal are ubiquitous across all drugs and which vary from drug to drug?
Affective symptoms (anxiety, chronic irritability, emotional pain, dysphoria, loss of interest in natural rewards) are universal
Somatic symptoms (eg felt in the body, malaise, autonomic) vary depending on the drug
What is the opponent process theory?
When you first experience a drug, the “opponent process” begins adapting and breaking down the drug
After it is metabolised the opponent process persists, leading to withdrawal
Chronic drug users possess a much stronger opponent process, meaning there is a stronger adaptive response (tolerance, chasing the first high), and more severe withdrawal as well
What are the 2 phenomena the oppenent process theory can’t explain?
“Subjects take drugs of abuse to fix the problem that the drug caused [withdrawal]” - George Koob
- However, people still relapse after prolonged abstinence (long after the opponent process has been eradicated)
- Incubation of drug-seeking (increase in craving for cocaine after withdrawal)
Describe the model of relapse seen in class
Reinstatement of drug-seeking in rats:
Train rat to press button for cocaine, then take cocaine away
During withdrawal, give cocaine for free, lever presses shoot back up
How was incubation of cocaine craving tested after withdrawal, and what were the results?
Rats were trained to lever-press for cocaine (IV) when a house light signalled it was available
The rats were then withdrawn from the cocaine in home cages for a different amounts of time
Then, the rats were retested with the light on
Saw that number of lever presses increase as time passes (the longer they waited the more likely they were to respond)
Does the increase in cocaine craving over time last forever?
No
There is a peak around 1-3 months then it drops off
What is the biggest shortcoming of most IVSA studies?
They measure the reinforcing effects of drugs, not necessarily addiction (Sherlock holmes was not an addict)
Define drug sensitization
The opposite of tolerance: The same amount of drug causes an increased effect (typically measured in locomotor activity)
eg rats given amphetamine worked much harder in PR IVSA for cocaine
True/False? All drugs have been observed show sensitization
False, eg morphine causes tolerance to heroin
How was ‘pleasure’ dissociated from ‘highness’?
subjects were given one of 3 pills (placebo, low dose meth, high dose meth) and asked how high they felt
They were given the choice between another pill (the same they’d been given) or a dollar
Results showed that only the high dose meth made them feel high (“pleasurable”), but both doses were equally reinforcing
Is DA required for the euphoria of cocaine? How was this tested?
No
Patients given amphetamine, then either nothing or Pimozide (DA antagonist)
No discernible difference
