Behavioural Pharmacology

Question 1

What is pharmacology?

Answer 1

The branch of medicine that deals with the uses, effects, and modes of actions of drugs.

Question 2

What is pharmacokinetics?

Answer 2

Subfield of pharmacology death with the absorption, distribution, biotransformation and excretion of drugs.

Question 3

What is pharmacodynamics?

Answer 3

Subfield of pharmacology dealing with the study of the biochemical effects of drugs and their mechanism of action.

Question 4

What is behavioural pharmacology?

Answer 4

The study of the relationship between the pharmacological actions of drugs and their effects on behaviour and psychological function.

Question 5

Why not just experiment using humans?

Answer 5

Largely because of more severe ethical limitations, especially when dealing with drug-naive subjects. Don’t know which direction the effect is - could be another reason that causes a change in the frontal cortex, which led them to become an addict. Could be an addict and have changes in the prefrontal cortex, but the two do not have to be related.

Question 6

What is primary evaluation?

Answer 6

Start with observation of simple “unconditioned” behaviours. Analyse what effect the drug has in terms of locomotor activity, balance, posture, eating and drinking, circadian cycles etc.

Question 7

What is the rota-rod test?

Answer 7

Test of balance and motor function. Measures the ability too the animal as a function of the drug they’ve taken to maintain their balance.

Question 8

What are effects of drugs on spontaneous behaviour?

Answer 8

Lyon and Robbins - Looked at measures of sleep, social investment, grooming and feeding relative to amphetamine. Increase dose leads to radical change in how the animal is spontaneously engaged in an activity. Get potent increases in rearing and locomotion - animals become hyperactive. Drugs do not create new behaviours - they alter the probability of behaviours already in the organisms’ repertoire.

Question 9

What is the tail-flick test?

Answer 9

Place animal on a platform, apply heat source to tail, have a dimmer so can increase the heat source, and measure the time it takes until the animal flicks its tail away. Highly predictive of analgesic effects in humans.

Question 10

What is the hot plate test?

Answer 10

Place animal on platform and the whole platform is heating up, test how long it takes for the animal to lift its leg. If drug increases the time, this indicates analgesic effects in humans.

Question 11

What is the elevated plus maze?

Answer 11

A test of anxiety. Measure the amount of time that rodents spend in the bright, exposed maze arms compared to the dark, sheltered maze arms. Highly predictive of anxiolytic efficacy in humans (e.g. benzodiazepines) - increases willingness to explore open arms.

Question 12

What is the radial arm maze?

Answer 12

Use in a variety of memory tests. Give the animal a problem to figure out to find the food. Give simple task of having to remember what you did a short while ago. Looking at cognitive effects, spatial working memory. See if a drug has a detrimental or positive effect on this.

Question 13

What is the morris walter maze?

Answer 13

A large round tank of water, in a room with various external cues providing navigation cues. One location where animal can stand. Measure time needed to find the platform, the path length, and the percentage time spent searching at the correct location.

Question 14

What is drug discrimination?

Answer 14

A method to ‘ask’ animals about the interoceptive cues associated with different drugs. If inject with saline, press left lever to get reward. If inject with cocaine, press right lever to get reward. This shows that the animal is aware of the effect of the drug, as if they press the right lever they feel the effect of cocaine. See similar curve on drug discrimination curve when studying cocaine and amphetamine. Cocaine and amphetamine produces similar psychological and physiological responses, but the difference is that amphetamine lasts much longer. But - drugs are complex (dose, route of administration, individual, etc.)

Question 15

What are measures of abuse potential?

Answer 15

Comparing drugs via relief of withdrawal symptoms. Steps: produce physical dependence with prototypical drug (e.g. propane), then withdraw (either remove drug or give opioid antagonist to produce withdrawal) and give drug test. IF blocks withdrawal symptoms will probably produce similar dependence syndrome. However, not conclusive, as withdrawal is not conclusively linked to addiction.

Question 16

How do we examine the reinforcing/incentive
properties of drugs (“will you work for it?”; “do
you ‘want’ it?”)

Answer 16

Conditioned place preference learning
‣ Drug self-administration
‣ Models of relapse

Question 17

How are drugs reinforcers?

Answer 17

Positive reinforcement: presentation increases the probability of the preceding behaviour.
Negative reinforcement: removal increases the probability of the preceding behaviour. Avoiding something bad (e.g. taking a drug to make you less anxious).
Punishment: presentation decreases the probability of a behaviour.
A single drug can have all three effects at once.

Question 18

What is conditioned place preference? (CPP)

Answer 18

Two distinct chambers, place animal in chamber one day and give it a drug (e.g. cocaine). Next day put the animal in another environment and get it nothing. If drug has reinforcing effects, the animal will go in the environment where they experienced this. Measuring the memory of the drug rather than the rewarding effect when it is in your system.

Question 19

What are advantages of CPP?

Answer 19

Fairly simply procedure. Limited effort required (subjects learn preference quickly). Test in non-drug state (avoids ‘side-effects’)

Question 20

What are disadvantages of CPP?

Answer 20

Not measuring the drug reward itself, but rather the rewarding effects of ‘secondary reward’ (drug-paired context). Psychological and brain mechanisms poorly understood.

Question 21

What is the skinner box?

Answer 21

When press lever is releases a bit of the drug that is transmitted via n IV. Not just how much they press, but how often - is it out of control or is it in regular intervals? This varies depending on pharmacokinetic factors. Gold standard because drugs that humans and animals will readily self-administer.

Question 22

What is drug self-administration?

Answer 22

Drugs that maintain self-administration are amphetamines, barbiturates, cocaine, codeine, ethanol, fentanyl, heroin, MDMA, morphine, nicotine, THC etc. Drugs that don’t are aspirin, lidocaine, LSD. One exception where humans self-administer and animals don’t are hallucinogenics. Nearly all drugs that people abuse, animals will self-administer. High predictive validity.

Question 23

What are ratio schedules of reinforcement?

Answer 23

Fixed Ratio (FR) - reinforcement after every n responses. Majority of studies use this, i.e. reinforcement after every response or for every 5 responses. 
Variable Ratio (VR) - number of presses required is unpredictable, but varies around some mean. e.g. VR15 = reinforcement on average every 15
responses (e.g. between 10 and 20)

Question 24

What are interval schedules of reinforcement?

Answer 24

Fixed Interval (FI)- reinforcement given when first press after a fixed delay,
e.g. FI-2min - reinforcement for 1st press every 2 min
Variable Interval (VI) - reinforcement given when first press after a varying
delay around a mean, e.g. VI-4min - reinforcement for 1st press after 4 min
on average (e.g. between 4 and 6 min).

Question 25

What happens when you use different schedules of reinforcement?

Answer 25

Different schedules = different behaviours. FR schedules tend to produce steady working for drug, FI schedules produce a more “scalloped” plot. See that the animal learns the time intervals that they will receive the drug, so tailor their response to adhere to this. Changes pattern of responding.

Question 26

How to check that self-administration is really “working for drug”?

Answer 26

Animals give themselves drug at intervals (via pressing lever). See an extinction burst - take the drug away and get a jump in responding - frustration effect. Tricks to make sure the animal is properly responding to the drug, and not responding for another reason.

Question 27

Why do you get an inverted-U-shaped curve on ‘simple’ ratio/interval schedule?

Answer 27

Looking at the dose effect curve, get a linear increase as you increase the dose, but there is a tipping point - all of a sudden see a decrease in responding. Why? - satiety, ‘preferred’ drug level (titration), incapacitation, loss of reward. If look at dose depending on the amount of cocaine they’re actually getting, get a linear increase.

Question 28

How to investigate a loss of reward for drugs?

Answer 28

Give lesion to remove dopamine in the brain, and the animal stops taking the drug - the drug isn’t rewarding anymore. After time, see a recovery of the response - this is to do with neuroplasticity. This shows dopamine is necessary for drug reward. But, a DA antagonist increases amphetamine self-administration. When take away dopamine the animal is compensating for it by taking more drug.

Question 29

What to look for on the dose-response (DR) curve?

Answer 29

Ambiguous measure - need to know where you are on the
dose-response (DR) curve
• If on the ascending part of the DR curve, decrease in responding may indicate decrease in reinforcement
• If on descending part of the DR curve, decrease in responding may indicate increase in reinforcement.
Many factors other than rewarding effects of the drug determine response rates, including motor side-effects of the drug, satiation effects, etc.

Question 30

What are progressive ratio schedules?

Answer 30

Looking at how far they are willing to go to get next fix. First time they have to press the lever once, then twice, then 4 times and so on. Measuring the breakpoint - the point at which the animal will stop trying to receive the drug. Advantage that much less drug is consumed so lower chance of motor side-effects
(incapacitation) and satiation effects. But, may produce extinction of learning.

Question 31

What are second-order schedules?

Answer 31

Effort is to reduce the amount of drug the animal is getting into their system. Mixed schedule - has to press 30 times for yellow light, then after some time pressing they get a bit of cocaine. Letting the animal press for a reminder of the cocaine. Can support large amounts of
lever pressing (“drug-seeking”) with little or no drug in system.

Question 32

What is the reinstatement model of drug relapse?

Answer 32

Devised methods to model relapse behaviour - what is it that happens to people that makes them resume drug taken after a long period of not taking it at all? After extinction has occur - is it exposure to drug related environment? Exposure to stressors?

Question 33

What did Shalev et al. 2002 find out about drug reinstatement?

Answer 33

Animals that used to take heroin, but went past the point of extinction. If get a little dose, it makes them seek it again. It is not drug specific - giving any drug makes you want the heroin again, e.g. cocaine and amphetamine. However, if give cocaine-trained rats heroin, they don’t look for cocaine again.

Question 34

What are tests for relapse/reinstatement?

Answer 34

1.Extinguish responding
2.Present stimulus and see if
reinstate responding
(under extinction conditions)
Stimuli that reinstate
responding:
1.Drug itself (drug prime)
2.Drug cue
3.Drug context
4.Stress

Question 35

What are factors that affect drug self-administration?

Answer 35

Dose, schedule of reinforcement, response requirement, response requirement, response type, stress, conditioned stimuli, prior experience with the drug, genes, gender, availability of other reinforcers, prior living conditions, hunger/thirst, length of withdrawal.

Question 36

How do you tell if a rat that is self-administering drugs is ‘addicted’?

Answer 36

Put in a chamber and can press a lever to get a drug, after a certain amount of time they are taken out. Another group are in the chamber for a longer time. The second group started to escalate their drug intake - began to lose control.

Question 37

What are extended access models?

Answer 37

• Looked at result in relation to addiction criteria in the DSM-IV. Looked at four measures

1. Drug seeking (even during periods of no drug availability) – 1 hour they stopped taking, but the long access animals kept pressing, despite the fact there was no drug
2. Resistance to punishment (taking drugs even when paired with electric shocks) - Short access animals didn’t/much less, long access kept pressing even though they got a shock
3. Increased drug motivated (elevated break point in progressive ratio schedule) - Long access animals willing to press for a longer time
4. Relapse (reinstatement of drug taking following extinction) - Long access much more susceptible to reinstatement