Drug Addiction

Question 1

What is the putative definition for Drug addiction?

Answer 1

A chronic neuobiological disease

Question 2

Define the addiction cycle and its 3 stages

Answer 2

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)

Question 3

What was Heyman’s Hypothesis for drug addiction?

Answer 3

He views addiction as resulting from suboptimal everyday decision making

“Temporally myopic view of the available alternatives”

Question 4

What are the 3 animal models of testing addiction learned in class?

Answer 4

Intracranial Self Stimulation (ICSS)
Intravenous Self Administration (IVSA)
Conditioned place preference (CPP)

Question 5

Describe the procedure of ICSS testing

Answer 5

Mouse has a microdialysis array set up that releases drug when the rat presses a lever

Question 6

Where does ICSS release the drug in the brain?

Answer 6

In the Nucleus Accumbens

Along with Ventral Tegmental Area, forms the Mesolimbic Dopamine System

Question 7

How can ICSS test for a rat’s drug threshold?

Answer 7

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

Question 8

What drug caused a decrease in rats’ threshold during ICSS? What does this imply?

Answer 8

d-Amphetamine

Exerts a reinforcer-enhancing effect (not saying amphetamine is more rewarding, just makes the brain more sensitive to rewards)

Question 9

Describe the procedure of testing IVSA. Why are there two levers?

Answer 9

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

Question 10

What does the unit/dose per dose graph show?

Answer 10

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)

Question 11

Describe the results of IVSA testing with cocaine on rats given pimozide (a DA antagonist)

Answer 11

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

Question 12

Describe the Progressive Radio reinforcement schedule for IVSA

Answer 12

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

Question 13

Describe the results of PR testing on rats with varying levels of cocaine/dose

Answer 13

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

Question 14

Describe the testing procedures for Conditioned place preference (CPP)

Answer 14

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

Question 15

What were Dr. White’s results when testing CPP in rats with amphetamine in different locations of the brain?

Answer 15

Amphetamine only increased CPP when it was administered to the Nucleus Accumbens

Question 16

What is an alternative method to CPP and what drawback is common to both?

Answer 16

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)

Question 17

Why is addiction complex?

Answer 17

Many factors go into it

Question 18

What symptoms of withdrawal are ubiquitous across all drugs and which vary from drug to drug?

Answer 18

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

Question 19

What is the opponent process theory?

Answer 19

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

Question 20

What are the 2 phenomena the oppenent process theory can’t explain?

Answer 20

“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)

Question 21

Describe the model of relapse seen in class

Answer 21

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

Question 22

How was incubation of cocaine craving tested after withdrawal, and what were the results?

Answer 22

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)

Question 23

Does the increase in cocaine craving over time last forever?

Answer 23

No

There is a peak around 1-3 months then it drops off

Question 24

What is the biggest shortcoming of most IVSA studies?

Answer 24

They measure the reinforcing effects of drugs, not necessarily addiction (Sherlock holmes was not an addict)

Question 25

Define drug sensitization

Answer 25

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

Question 26

True/False? All drugs have been observed show sensitization

Answer 26

False, eg morphine causes tolerance to heroin

Question 27

How was ‘pleasure’ dissociated from ‘highness’?

Answer 27

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

Question 28

Is DA required for the euphoria of cocaine? How was this tested?

Answer 28

No

Patients given amphetamine, then either nothing or Pimozide (DA antagonist)

No discernible difference